Full data view for gene PLG

Information The variants shown are described using the NM_000301.3 transcript reference sequence.

113 entries on 2 pages. Showing entries 1 - 100.
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Effect     

Exon     

AscendingDNA change (cDNA)     

RNA change     

Protein     

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Classification method     

Clinical classification     

DNA change (genomic) (hg19)     

DNA change (hg38)     

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ISCN     

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Variant remarks     

Reference     

ClinVar ID     

dbSNP ID     

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Frequency     

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Methylation     

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Disease     

ID_report     

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Gender     

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VIP     

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Owner     
-?/. 1 c.12G>A r.(?) p.(Lys4=) Unknown - likely benign g.161123348G>A - PLG(NM_000301.3):c.12G>A (p.K4=) - PLG_000042 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. 1i c.50-15A>T r.(=) p.(=) Unknown - likely benign g.161127424A>T g.160706392A>T PLG(NM_000301.3):c.50-15A>T - PLG_000015 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. 2 c.110C>G r.(?) p.(Thr37Ser) Unknown - likely benign g.161127499C>G g.160706467C>G PLG(NM_000301.3):c.110C>G (p.T37S) - PLG_000016 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.112A>G r.(?) p.(Lys38Glu) Unknown - VUS g.161127501A>G g.160706469A>G PLG(NM_000301.3):c.112A>G (p.K38E), PLG(NM_000301.5):c.112A>G (p.K38E) - PLG_000017 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. - c.112A>G r.(?) p.(Lys38Glu) Unknown - pathogenic g.161127501A>G g.160706469A>G PLG(NM_000301.3):c.112A>G (p.K38E), PLG(NM_000301.5):c.112A>G (p.K38E) - PLG_000017 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.112A>G r.(?) p.(Lys38Glu) Unknown - VUS g.161127501A>G g.160706469A>G PLG(NM_000301.3):c.112A>G (p.K38E), PLG(NM_000301.5):c.112A>G (p.K38E) - PLG_000017 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/+ 2 c.112A>G r.(?) p.(Lys38Glu) Both (homozygous) ACMG pathogenic (recessive) g.161127501A>G g.160706469A>G K19E - PLG_000017 tPA-mediated activation assays could predict the clinical outcome for Lys38Glu carriers, but fibrin-independent uPA-mediated assays could not: p.Lys38Glu variant is likely not to be able to efficiently engage fibrin, with a subsequent short half-life. Lys19 is a very conserved residue among primates. One possible mechanism for plasminogen deficiency resulting from Lys to Glu substitution could be its location in the N-terminus region. In Glu1-PLG, p.Lys38Glu variant may lead to a relaxed conformational state, which is easier to activate and degrade. Journal: Tefs 2006 Journal: Bourrienne 2020 ClinVar-RCV000014551.38 rs73015965 Germline yes 0.00282 - - - DNA SEQ blood - deficiency, plasminogen, type I - Journal: Tefs 2006 Five independent families with homozygous affected patients have been shown as carrying a c.112A>G variant. Heterozygous carriers of these 5 families are not affected. Three independent families with compound heterozygous affected patients have been shown as carrying both c.112A>G and c.1468C>T variants. - - - - - - - - 8 Christian Drouet
+?/+? 2 c.112A>G r.(?) p.(Lys38Glu) Parent #1 ACMG pathogenic (recessive) g.161127501A>G g.160706469A>G - - PLG_000017 Variants c.112A>G and c.1468C>T have been found carried by compound heterozygous affected patients Journal: Tefs 2006 ClinVar-RCV000014551.38 rs73015965 Germline yes 0.00282 - - - DNA ? blood - deficiency, plasminogen, type I - Journal: Tefs 2006 Five independent families with homozygous affected patients have been shown as carrying a c.112A>G variant. Heterozygous carriers of these 5 families are not affected. Three independent families with compound heterozygous affected patients have been shown as carrying both c.112A>G and c.1468C>T variants. - - - - - - - - 8 Christian Drouet
-/. - c.169G>A r.(?) p.(Glu57Lys) Unknown - benign g.161127558G>A - PLG(NM_000301.3):c.169G>A (p.E57K) - PLG_000059 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/+ 2i c.185+1G>T r.spl? p.? Unknown ACMG pathogenic g.161127575G>T g.160706543G>T - - PLG_000063 - - ClinVar-RCV000403862.4 rs886042477 Germline - 0.00005 - - - DNA ? blood - deficiency, plasminogen, type I - - - - - - - - - - - 1 Christian Drouet
-?/. - c.185+15G>A r.(=) p.(=) Unknown - likely benign g.161127589G>A g.160706557G>A PLG(NM_000301.3):c.185+15G>A - PLG_000038 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.186-9G>A r.(=) p.(=) Unknown - likely benign g.161128723G>A - PLG(NM_000301.3):c.186-9G>A - PLG_000052 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/-? 3 c.266G>A r.(?) p.(Arg89Lys) Unknown - VUS g.161128812G>A g.160707780G>A 266G>A - PLG_000049 Variant predicted to be damaging but not as yet correlated with any pathogenic effect. Arg70 is one of the key residues of the PLG AP domain identified by X-ray crystallography to form important bonds for maintenance of PLG conformation. This residue coordinates with K4 and K5 domains through interactions with Asp413 and Asp534. A Arg to Lys transition is not expected to disrupt this coordinates between electropositive and electronegative residues. PubMed: Duvvari 2016 - rs143079629 Germline - - - - - DNA SEQ, SEQ-NG - WES retinal disease Pat11AB PubMed: Duvvari 2016 patient - - Netherlands white - - - - 1 LOVD
+/+? - c.266G>C r.(?) p.(Arg89Thr) Unknown - VUS g.161128812G>C g.160707780G>C - - PLG_000062 Arg70 is a key residue identified by X-ray crystallography in PLG AP domain to form important bonds for maintenance of the PLG conformation. It coordinates with K4 and K5 domains through interactions with Asp413 and Asp534. A Arg to Thr transition is predicted as possibly damaging by disrupting the PLG closed conformation with a Thr residue being unable to interact with K4 and K5. Variant p.(Arg89Thr) has been flagged as having a potential association with plasminogen deficiency type I and hereditary angioedema with normal C1-INH function - enhanced PLG activation to plasmin and subsequent lower half-life of the zymogen. - ClinVar-RCV001334374.1 rs143079629 Germline - - - - - DNA SEQ blood - deficiency, plasminogen, type I - - - - - - - - - - - 1 Christian Drouet
-?/. 3i c.293-6C>A r.(=) p.(=) Unknown - likely benign g.161132103C>A g.160711071C>A PLG(NM_000301.3):c.293-6C>A, PLG(NM_000301.5):c.293-6C>A - PLG_000034 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.293-6C>A r.(=) p.(=) Unknown - likely benign g.161132103C>A - PLG(NM_000301.3):c.293-6C>A, PLG(NM_000301.5):c.293-6C>A - PLG_000034 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. 4 c.330C>T r.(?) p.(Asn110=) Unknown - benign g.161132146C>T g.160711114C>T - - PLG_000018 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.459G>A r.(?) p.(Arg153=) Unknown - likely benign g.161134069G>A g.160713037G>A PLG(NM_000301.3):c.459G>A (p.R153=) - PLG_000019 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.471C>T r.(?) p.(Asn157=) Unknown - likely benign g.161134081C>T g.160713049C>T PLG(NM_000301.3):c.471C>T (p.N157=) - PLG_000001 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. - c.489G>A r.(?) p.(Trp163Ter) Unknown - pathogenic g.161134099G>A g.160713067G>A PLG(NM_000301.3):c.489G>A (p.W163*) - PLG_000020 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.581A>T r.(?) p.(Asp194Val) Unknown - likely benign g.161135859A>T - PLG(NM_000301.3):c.581A>T (p.D194V) - PLG_000053 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.598A>G r.(?) p.(Thr200Ala) Unknown - VUS g.161135876A>G g.160714844A>G PLG(NM_000301.3):c.598A>G (p.T200A) - PLG_000039 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/? 6 c.598A>G r.(?) p.(Thr200Ala) Unknown - likely pathogenic g.161135876A>G g.160714844A>G - - PLG_000039 The variant c.598A>G could lead to clinical angioedema phenotype. Probably the association of HAE with cutis laxa might explain the recurrent attacks of swelling. Journal: de Albuquerque Campos 2023 - - Germline - - - - - DNA SEQ-NG - - HAE4 - Journal: de Albuquerque Campos 2023 - F no Brazil - - - - - 1 Christian Drouet
-/. 6i c.669-14T>G r.(=) p.(=) Unknown - benign g.161137663T>G g.160716631T>G PLG(NM_000301.5):c.669-14T>G - PLG_000002 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.669-14T>G r.(=) p.(=) Unknown - benign g.161137663T>G g.160716631T>G PLG(NM_000301.5):c.669-14T>G - PLG_000002 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/+ 7 c.704G>A r.(?) p.(Arg235His) Both (homozygous) ACMG pathogenic (recessive) g.161137712G>A g.160716680G>A c.780G>A; c.[704G>A];[704G>A] - PLG_000064 Both parents and an older sister are clinically healthy. Plasminogen functional activity in patient plasma was only 6% (normal range, 80% to 120%); heterozygous carriers exhibit 40% to 76% plasminogen activity. Variant p.Arg235His shows significant secretion impairment and enhanced degradation when expressed in COS-7 cells. Arg216 residue is located proximal to strictly conserved Cys residues in the kringle K2 domain and forms a network of H-bonds that stabilize the K2 domain. The disruption of the Arg residue in this position may impairs proper folding of the domains and lead to poor secretion. Journal: Schuster 1997 Journal: Tefs 2006 ClinVar-RCV000014545.26 rs121918030 Germline yes 0.0000071 - - - DNA ? - - deficiency, plasminogen, type I - Journal: Tefs 2006 - - - - - - - - - 1 Christian Drouet
?/. 7 c.712G>A r.(?) p.(Asp238Asn) Unknown - VUS g.161137720G>A - PLG(NM_000301.5):c.712G>A (p.D238N) - PLG_000060 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.758G>A r.(?) p.(Arg253His) Unknown - VUS g.161137766G>A g.160716734G>A PLG(NM_000301.3):c.758G>A (p.R253H) - PLG_000035 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.771T>C r.(?) p.(Cys257=) Unknown - benign g.161137779T>C g.160716747T>C PLG(NM_000301.5):c.771T>C (p.C257=) - PLG_000003 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.771T>C r.(?) p.(Cys257=) Unknown - benign g.161137779T>C g.160716747T>C PLG(NM_000301.5):c.771T>C (p.C257=) - PLG_000003 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. 7 c.782G>A r.(?) p.(Arg261His) Unknown - VUS g.161137790G>A g.160716758G>A PLG(NM_000301.3):c.782G>A (p.R261H) - PLG_000004 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.942C>T r.(?) p.(Phe314=) Unknown - benign g.161139480C>T g.160718448C>T PLG(NM_000301.5):c.942C>T (p.F314=) - PLG_000021 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. 8 c.942C>T r.(?) p.(Phe314=) Unknown - benign g.161139480C>T g.160718448C>T PLG(NM_000301.5):c.942C>T (p.F314=) - PLG_000021 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.950+14G>A r.(=) p.(=) Unknown - benign g.161139502G>A g.160718470G>A PLG(NM_000301.5):c.950+14G>A - PLG_000005 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. 8i c.950+14G>A r.(=) p.(=) Unknown - benign g.161139502G>A g.160718470G>A PLG(NM_000301.5):c.950+14G>A - PLG_000005 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. 8i c.950+16T>C r.(=) p.(=) Unknown - VUS g.161139504T>C g.160718472T>C PLG(NM_000301.3):c.950+16T>C - PLG_000022 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. 8i c.950+16T>C r.(=) p.(=) Unknown - likely benign g.161139504T>C - PLG(NM_000301.3):c.950+16T>C - PLG_000022 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. 9 c.974G>A r.(?) p.(Arg325His) Unknown - VUS g.161139748G>A g.160718716G>A PLG(NM_000301.3):c.974G>A (p.R325H) - PLG_000023 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. 9 c.985G>A r.(?) p.(Gly329Arg) Unknown - VUS g.161139759G>A g.160718727G>A PLG(NM_000301.3):c.985G>A (p.G329R) - PLG_000036 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Maternal (confirmed) ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000046 - Journal: Bork 2020 ClinVar-RCV001507288.6 rs889957249 Germline - 0.00004 (gnomAD_exome), 0.00003 (gnomAD) - - - DNA SEQ blood - HAE4 - Journal: Bork 2020 One family with compound heterozygous individuals and 12 affected patients - - Germany - - - - - 12 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000046 ACMG classification: Characterized as Class 5 (pathogenic) by ghardy Bork 2018: 13 families with 60 affected individuals Bork 2023: Occurrence of only one symptomatic patient per family, who had no family history of angioedema but who had symptom-free relatives carrying the same HAE-linked c.988A>G variant. Hintze 2023 concluded that the kallikrein-kinin system is bypassed in HAE-PLG. Structural modeling and in vitro assays confirmed the PLG mutation c.988A>G; p.Lys330Glu to be a gain of function mutation resulting in an increased bradykinin release by direct HK cleavage. Bork 2025: Hypertension risk for carriers of c.988A>G variant. Journal: Bork 2018 Journal: Bork 2020 Journal: Bork 2023 Journal: Hintze 2023 Journal: Bork 2025 ClinVar-RCV001507288.6 rs889957249 Germline/De novo (untested) yes 0.00004 (gnomAD_exome), 0.00003 (gnomAD), 6.98e-06 (gnomAD v3) - - - DNA SEQ blood - HAE4 - Journal: Bork 2018 Journal: Bork 2023 Journal: Hintze 2023 Bork 2018: Thirteen families with 60 affected individuals Bork 2023: Six German pedigrees have been found to carry a c.988A>G; solitary German carriers (n=6) Hintze 2023: a German pedigree with 8 affected individuals - no Germany - - - - - 74 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Both (homozygous) ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 Homozygous carrier of p.(Lys330Glu) displays an abnormal glycosylation pattern with ~60% of PLG type I and ~40% of PLG type II. Homozygous or heterozygous (n = 8) carriers of p.(Lys330Glu) display a significantly high susceptibility to zymogen activation by streptokinase and urokinase. Journal: Germenis 2018 Journal: Parsopoulou 2020 ClinVar-RCV001507288.6 rs889957249 Germline yes 0.00003 (gnomAD); 0.000004 (1/251070, GnomAD_exome) - - - DNA SEQ-NG-IT blood - HAE4 - Journal: Germenis 2018 First family with a homozygous proband for a c.988A>G variant and 3 heterozygous carriers, incl one symptomatic female individual - - Greece - - - - - 4 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Both (homozygous) ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000046 Homozygous or heterozygous (n = 8) carriers of p.(Lys330Glu) display a significantly high susceptibility to the PLG activation by streptokinase and urokinase Journal: Germenis 2018 Journal: Parsopoulou 2020 ClinVar-RCV001507288.6 rs889957249 Germline yes 0.000004 (gnomAD_exome); 0.00003 (gnomAD) - - - DNA SEQ-NG-IT - - HAE4 - Journal: Germenis 2018 A single pedigree has been found as carrying a c.988A>G variant; the female proband is a homozygous carrier, 2 heterozygous carriers have been found asymptomatic. F ? Greece - - - - - 3 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Bodian 2019 - - Germline/De novo (untested) ? 0.000004 (1/251070, GnomAD_exome) - - - DNA SEQ-NG-I blood - HAE4 - Journal: Bodian 2019 - F - United States - - - - - 1 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Recke 2019 - - Germline ? 0.000004 (1/251070, GnomAD_exome) - - - DNA SEQ blood - HAE4 - Journal: Recke 2019 - - no Germany - - - - - 6 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Belbezier 2018 - - Germline yes 0.000004 (1/251070, GnomAD_exome) - - - DNA SEQ blood - HAE4 - Journal: Belbezier 2018 Three kindreds have been reported as carrying a c.988A>G variant, with 12 affected individuals - no France - - - - - 12 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000046 The heterozygous carriers of the family present with two bands of PLG type I and PLG type II approximately equal intensity and a susceptibility to zymogen activation. The Lys to Glu substitution introduces a Lys-binding site into the PLG kringle 3 domain, propably altering binding to kininogens. Plg residue 311 is Glu in most mammals. Glu311 in patients with HAE represents reversion to the ancestral condition. Substantial BK generation occurs during Plg-Glu311 cleavage of human HK, but not mouse HK. Mouse Plg, which has Glu311, did not liberate BK from human kininogens more rapidly than human PLG-Lys311. This indicates Glu311 is pathogenic in the context of human PLG when human kininogens are the substrates. Journal: Parsopoulou 2020 Journal: Dickeson 2022 ClinVar-RCV001507288.6 rs889957249 Germline yes 0.00003 (gnomAD); 0.000004 (gnomAD_exome) - - - DNA SEQ-NG-IT blood - HAE4 - Journal: Parsopoulou 2020 A Spanish family with 5 heterozygous carriers of a c.988A>G variant, incl 3/5 symptomatic individuals - no Spain - - - - - 3 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Farkas 2021 ClinVar-RCV001507288.6 rs889957249 Germline no 0.000004 (gnomAD_exome) - - - DNA SEQ blood - HAE4 - Journal: Farkas 2021 Hungarian pedigree with a single symptomatic carrier of a c.988A>G variant in the PLG gene F - Hungary - - - - - 1 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Yakushiji 2018 ClinVar-RCV001507288.6 rs889957249 Germline ? 0.000004 (1/251070, GnomAD_exome) - - - DNA SEQ blood - HAE4 - Journal: Yakushiji 2018 Two Japanese pedigrees have been found as carrying a c.988A>G variant in the PLG gene Family 1 (n=2) Family 2 (n=2) - - Japan - - - - - 4 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 The proband is also carrier of a c.931T>C;p.(Cys311Arg) variant in the CPN1 gene, predicted as deleterious Journal: Germenis 2018 ClinVar-RCV001507288.6 rs889957249 Germline/De novo (untested) ? 0.000004 (1/251070, GnomAD_exome) - - - DNA SEQ-NG-IT blood - HAE4 - Journal: Germenis 2018 - F - Bulgaria - - - - - 1 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Manto 2021 ClinVar-RCV001507288.6 - Germline yes - - - - DNA SEQ blood - HAE4 - Journal: Manto 2021 10 families, with 14 affected carriers, have been reported as carrying a PLG variant c.988A>G - - Russia - - - - - 14 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Maternal (inferred) ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 third japanese pedigree carrying c.988A>G variant and presenting with angioedema attacks; 3 carriers (1 female, 2 male) are asymptomatic PubMed: Yakushiji 2023, Journal: Yakushiji 2023 ClinVar-RCV001507288.6 rs889957249 Germline yes 0.0000029 - - - DNA SEQ blood - HAE4 FamPatII1 PubMed: Yakushiji 2023, Journal: Yakushiji 2023 3-generation family, 5 affected (4 female, 1 male); 3 carriers (1 female, 2 male) are asymptomatic F no Japan - - - - - 5 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Maternal (confirmed) ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 Compound heterozygous proband carrying PLG c.988A>G;p.(Lys330Glu) and F12 c.1681-1G>A variants Journal: Hintze 2023 ClinVar-RCV001507288.6 rs889957249 Germline yes 0.00003 (gnomAD); 0.000004 (1/251070, GnomAD_exome) - - - DNA SEQ blood - HAE4 - Journal: Hintze 2023 A female proband carrying both variants PLG c.988A>G;p.(lys330Glu) and F12 c.1681-1G>A; 6 compound heterozygous affected individuals, 2 heterozygous affected individuals carrying a PLG variant F - Germany - - - - - 8 Christian Drouet
+/. 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G c.1100A>G - PLG_000045 The variant has been erroneously identified in the 3 families as c.1100A>G Journal: Dewald 2018 ClinVar-SCV002762862 rs889957249 Germline yes 0.00000708 - - - DNA SEQ blood - HAE4 Fam1-3 Journal: Dewald 2018 Three independent pedigrees have been shown as carrying the variant Family 1 (n=9), Family 2 (n=4), Family 3 (n=9) F - Germany - - - - - 22 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 A single female individuals carrying a c.988A>G variant Journal: Nakayama 2023 ClinVar-SCV002762862 rs889957249 Germline - 0.0000029 - - - DNA SEQ blood - HAE4 - Journal: Nakayama 2023 Single individual F no Japan - - - - - 1 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Katelaris 2023 - rs889957249 Germline yes - - - - DNA SEQ blood - HAE4 - Journal: Katelaris 2023 - F - Brazil white (Italy) - - - - 2 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 Treatment of attacks by tranexamic acid Journal: Friedman 2023 - - Germline yes - - - - DNA SEQ blood - HAE4 - Journal: Friedman 2023 A US family with a female proband is presenting with macroglossia, a mother with peripheral angioedema and a son died because of airway obstruction F - United States - - - - - 3 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Rozevska 2024 - - Germline yes - - - - DNA SEQ blood - HAE4 - Journal: Rozevska 2024 - - no Latvia - - - - - 1 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Adatia 2024 - - Germline - - - - - DNA SEQ blood - HAE4 - Journal: Adatia 2024 - - - Canada - - - - - 2 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Sugimoto 2025 ClinVar-RCV001507288.8 rs889957249 Germline yes 0.0000029 - - - DNA SEQ - - HAE4 - Journal: Sugimoto 2025 Single female individual affected F no Japan - - - - - 1 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 Two affected sisters Journal: Sugimoto 2025 ClinVar-RCV001507288.6 rs889957249 Germline yes 0.000004 - - - DNA SEQ blood - HAE4 - Journal: Sugimoto 2025 A single family with two affected sisters F no Japan - - - - - 2 Christian Drouet
+/+ 9 c.988A>G r.(?) p.(Lys330Glu) Unknown ACMG pathogenic g.161139762A>G g.160718730A>G - - PLG_000045 - Journal: Purina 2023 ClinVar-RCV001507288.6 rs889957249 Germline/De novo (untested) - - - - - DNA SEQ - - HAE4 - Journal: Purina 2023 The first HAE-nC1INH patient from Latvia with identified pathogenic variant in the PLG gene. F no Latvia - - - - - 1 Christian Drouet
-/. - c.1083A>G r.(?) p.(Gln361=) Unknown - benign g.161139857A>G g.160718825A>G PLG(NM_000301.5):c.1083A>G (p.Q361=) - PLG_000006 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.1083A>G r.(?) p.(Gln361=) Unknown - benign g.161139857A>G g.160718825A>G PLG(NM_000301.5):c.1083A>G (p.Q361=) - PLG_000006 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1098A>T r.(?) p.(Ala366=) Unknown - likely benign g.161143441A>T - PLG(NM_000301.3):c.1098A>T (p.A366=) - PLG_000058 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.1222C>T r.(?) p.(Arg408Trp) Unknown - benign g.161143565C>T - PLG(NM_000301.3):c.1222C>T (p.R408W) - PLG_000061 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. 10i c.1256+9T>C r.(=) p.(=) Unknown - benign g.161143608T>C g.160722576T>C PLG(NM_000301.5):c.1256+9T>C - PLG_000007 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.1256+9T>C r.(=) p.(=) Unknown - benign g.161143608T>C g.160722576T>C PLG(NM_000301.5):c.1256+9T>C - PLG_000007 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1259G>A r.(?) p.(Gly420Asp) Unknown - likely benign g.161152085G>A g.160731053G>A PLG(NM_000301.3):c.1259G>A (p.G420D) - PLG_000008 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1259G>A r.(?) p.(Gly420Asp) Unknown - likely benign g.161152085G>A g.160731053G>A PLG(NM_000301.3):c.1259G>A (p.G420D) - PLG_000008 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1281G>A r.(?) p.(Arg427=) Unknown - likely benign g.161152107G>A g.160731075G>A PLG(NM_000301.3):c.1281G>A (p.R427=) - PLG_000024 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1281G>A r.(?) p.(Arg427=) Unknown - likely benign g.161152107G>A g.160731075G>A PLG(NM_000301.3):c.1281G>A (p.R427=) - PLG_000024 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.1414G>A r.(?) p.(Asp472Asn) Unknown - benign g.161152240G>A g.160731208G>A - - PLG_000025 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1431C>T r.(?) p.(Ser477=) Unknown - likely benign g.161152257C>T - PLG(NM_000301.3):c.1431C>T (p.S477=) - PLG_000056 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/+ 12 c.1468C>T r.(?) p.(Arg490*) Parent #2 ACMG pathogenic (recessive) g.161152806C>T g.160731774C>T R471X - PLG_000066 Secretion kinetics of PLG variant Arg490Ter appears to be normal, but protein derived from truncated PLG variant was detectable as a 62-kDa band due to a lack of the PLG beta-chain and part of kringle 5 domain. Journal: Tefs 2006 ClinVar-RCV003555313.1 - Germline yes - - - - DNA ? blood - deficiency, plasminogen, type I - Journal: Tefs 2006 Five independent families with homozygous affected patients have been shown as carrying a c.112A>G variant. Heterozygous carriers of these 5 families are not affected. Three independent families with compound heterozygous affected patients have been shown as carrying both c.112A>G and c.1468C>T variants. - - - - - - - - 8 Christian Drouet
?/. - c.1469G>A r.(?) p.(Arg490Gln) Unknown - VUS g.161152807G>A g.160731775G>A PLG(NM_000301.3):c.1469G>A (p.R490Q), PLG(NM_000301.5):c.1469G>A (p.R490Q) - PLG_000009 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. 12 c.1469G>A r.(?) p.(Arg490Gln) Parent #1 - VUS g.161152807G>A g.160731775G>A - - PLG_000009 1 heterozygous, no homozygous; Clinindb (India) PubMed: Narang 2020 Journal: Narang 2020 ClinVar-RCV000625418.2 rs140537724 Germline - 1/2794 individuals - - - DNA arraySNP - Infinium Global Screening Array v1.0 ? - PubMed: Narang 2020, Journal: Narang 2020 analysis 2794 individuals (India) - - India - - - - - 1 Mohammed Faruq
?/. - c.1469G>A r.(?) p.(Arg490Gln) Unknown - VUS g.161152807G>A - PLG(NM_000301.3):c.1469G>A (p.R490Q), PLG(NM_000301.5):c.1469G>A (p.R490Q) - PLG_000009 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.1469G>A r.(?) p.(Arg490Gln) Unknown - VUS g.161152807G>A - PLG(NM_000301.3):c.1469G>A (p.R490Q), PLG(NM_000301.5):c.1469G>A (p.R490Q) - PLG_000009 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.1481C>T r.(?) p.(Ala494Val) Unknown - benign g.161152819C>T g.160731787C>T PLG(NM_000301.3):c.1481C>T (p.A494V) - PLG_000010 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.1481C>T r.(?) p.(Ala494Val) Unknown - benign g.161152819C>T - PLG(NM_000301.3):c.1481C>T (p.A494V) - PLG_000010 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1500G>A r.(?) p.(Thr500=) Unknown - likely benign g.161152838G>A g.160731806G>A PLG(NM_000301.3):c.1500G>A (p.T500=) - PLG_000026 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1503A>G r.(?) p.(Pro501=) Unknown - likely benign g.161152841A>G - PLG(NM_000301.3):c.1503A>G (p.P501=) - PLG_000043 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.1567C>T r.(?) p.(Arg523Trp) Unknown - VUS g.161152905C>T g.160731873C>T - - PLG_000027 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. 12 c.1567C>T r.(?) p.(Arg523Trp) Unknown - association g.161152905C>T g.160731873C>T - - PLG_000027 Located in the kringle 5 domain of plasminogen, the p.(Arg523Trp) product expression is decreased compared to the wild-type and has been associated with a protection of the carrier from ACEi angioedema. Journal: Ronald 2011PubMed: Mathey 2022, Journal: Mathey 2022 ClinVar-VCV000770367.4 rs4252129 Germline - - - - - DNA MIPsm blood - Healthy/Control - PubMed: Mathey 2022, Journal: Mathey 2022 - - - - - - - - - 1 Christian Drouet
+/+? - c.1571C>T r.(?) p.(Ala524Val) Unknown ACMG VUS g.161152909C>T g.160731877C>T - - PLG_000065 Conflicting observations: VUS to pathogenic Journal: Tefs 2006 ClinVar-RCV003901185.1 - Germline - - - - - DNA ? blood - deficiency, plasminogen, type I - Journal: Tefs 2006 - - - - - - - - - 1 Christian Drouet
?/. 14 c.1735G>A r.(?) p.(Gly579Arg) Unknown - VUS g.161157972G>A g.160736940G>A - - PLG_000047 - - VCV000988227.1 - Germline - 0.00026 (31/121370 alleles; ExAC) - - - DNA SEQ - - AHUS - - - - - Australia - - - - - 1 Christian Drouet
-?/. 14i c.1803-17C>A r.(=) p.(=) Unknown - likely benign g.161159553C>A g.160738521C>A PLG(NM_000301.3):c.1803-17C>A - PLG_000040 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/+ 15 c.1848G>A r.(?) p.(Trp616*) Parent #1 - pathogenic g.161159615G>A g.160738583G>A - - PLG_000037 1 heterozygous individual, no homozygous PubMed: Narang 2020, Journal: Narang 2020 ClinVar-RCV000014546.26 rs121918031 Germline - 1/2794 individuals - - - DNA arraySNP - Infinium Global Screening Array v1.0 ? - PubMed: Narang 2020, Journal: Narang 2020 analysis 2794 individuals (India) - - India - - - - - 1 Mohammed Faruq
+/+ 15 c.1848G>A r.(?) p.(Trp616*) Both (homozygous) ACMG pathogenic (recessive) g.161159615G>A g.160738583G>A c.1924G>A - PLG_000037 <5% plasminogen functional activity was found (normal range, 80% to 120%). Heterozygous healthy carriers exibit 15% to 66% plasminogen function. Journal: Schuster 1997 ClinVar-RCV000014546.26 rs121918031 Germline - - - - - DNA SEQ blood - deficiency, plasminogen, type I - Journal: Schuster 1997 - F yes Turkey - - - - - 1 Christian Drouet
+?/+? 15 c.1848G>A r.(?) p.(Trp616*) Parent #2 ACMG pathogenic (recessive) g.161159615G>A g.160738583G>A c.1924G>A; c.[1848G>A];[1848G>C] - PLG_000037 Affected compound heterozygous individual exhibits 15% plasminogen function. The heterozygous sibling exhibits 60% plasminogen function and is apparently healthy. PubMed: Schuster 1997 ClinVar-SCV000034797 rs121918031 Germline yes 1/2794 individuals - - - DNA SEQ - - deficiency, plasminogen, type I - PubMed: Schuster 1997 Single family with a compound heterozygous affected individual M - Germany - - - - - 1 Christian Drouet
+?/+? 15 c.1848G>C r.(?) p.(Trp616Cys) Parent #1 ACMG pathogenic (recessive) g.161159615G>C g.160738583G>C c.1924G>C; c.[1848G>A];[1848G>C] - PLG_000067 Affected compound heterozygous individual exhibits 15% plasminogen function. The heterozygous sibling exhibits 66% plasminogen function and is apparently healthy. PubMed: Schuster 1997 ClinVar-SCV000034797 rs121918031 Germline yes 0.0000014 - - - DNA SEQ - - deficiency, plasminogen, type I - PubMed: Schuster 1997 Single family with a compound heterozygous affected individual M - Germany - - - - - 1 Christian Drouet
-?/. - c.1852T>C r.(?) p.(Leu618=) Unknown - likely benign g.161159619T>C g.160738587T>C PLG(NM_000301.3):c.1852T>C (p.L618=) - PLG_000011 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. 15 c.1858G>A r.(?) p.(Ala620Thr) Maternal (confirmed) - VUS g.161159625G>A g.160738593G>A - - PLG_000057 The mother of the proband is a homozygous asymptomatic carrier of c.1858G>A variant. The prevalence of c.1858G>A homozygosity is predicted to be 0.0256-0.0543% of population of East Asian countries, suggesting that the homozygous PLG c.[1858G>A];[1858G>A] variant is not related to an increased risk of thrombosis Journal: Lee 2022 ClinVar-VCV000013574.4 rs121918027 Germline no 0.00083 - - - DNA SEQ blood - deficiency, plasminogen, type I - Journal: Lee 2022 - M - Korea - - - - - 1 Christian Drouet
-?/. 15i c.1877+4T>C r.spl? p.? Unknown - likely benign g.161159648T>C - PLG(NM_000301.3):c.1877+4T>C - PLG_000050 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.1878-17G>A r.(=) p.(=) Unknown - benign g.161160083G>A g.160739051G>A - - PLG_000028 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1878-6T>C r.(=) p.(=) Unknown - likely benign g.161160094T>C g.160739062T>C PLG(NM_000301.3):c.1878-6T>C - PLG_000012 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1878-6T>C r.(=) p.(=) Unknown - likely benign g.161160094T>C g.160739062T>C PLG(NM_000301.3):c.1878-6T>C - PLG_000012 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.1924G>C r.(?) p.(Glu642Gln) Unknown - VUS g.161160146G>C g.160739114G>C PLG(NM_000301.3):c.1924G>C (p.E642Q) - PLG_000029 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1935C>T r.(?) p.(Leu645=) Unknown - likely benign g.161160157C>T - PLG(NM_000301.3):c.1935C>T (p.L645=) - PLG_000044 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
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