Full data view for gene TSC2

The curator’s expert opinion on the classification of a variant, can be found in the
SUMMARY record. Regarding the classification, please note that where there are several
records of the same variant, the classification of that variant may differ depending on the
submitter’s conclusion.
Information The variants shown are described using the NM_000548.3 transcript reference sequence.

17 entries on 1 page. Showing entries 1 - 17.
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Effect     

Exon     

AscendingDNA change (cDNA)     

RNA change     

Protein     

P-domain     

Predict-BioInf     

Allele     

Classification method     

Clinical classification     

DNA change (genomic) (hg19)     

DNA change (hg38)     

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ISCN     

DB-ID     

Variant remarks     

Reference     

ClinVar ID     

dbSNP ID     

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Frequency     

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Methylation     

Template     

Technique     

Tissue     

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Disease     

ID_report     

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Owner     
-?/. - c.2476C>A r.(?) p.(Leu826Met) - - Unknown - likely benign g.2124321C>A g.2074320C>A TSC2(NM_000548.3):c.2476C>A (p.L826M), TSC2(NM_000548.5):c.2476C>A (p.L826M) - TSC2_000132 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.2476C>A r.(?) p.(Leu826Met) - - Unknown - likely benign g.2124321C>A g.2074320C>A TSC2(NM_000548.3):c.2476C>A (p.L826M), TSC2(NM_000548.5):c.2476C>A (p.L826M) - TSC2_000132 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.2476C>A r.(?) p.(Leu826Met) - - Unknown - benign g.2124321C>A g.2074320C>A TSC2(NM_000548.3):c.2476C>A (p.L826M), TSC2(NM_000548.5):c.2476C>A (p.L826M) - TSC2_000132 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. 22 c.2476C>A - p.Leu826Met Hamartin binding domain - Unknown - NA g.2124321C>A g.2074320C>A - - TSC2_000132 no effect on tuberin-hamartin interaction; rheb GTPase activity increased and S6 phosphorylation inhibited as seen with wt tuberin; S6K T389 phosphorylation not significantly higher than wild type TSC2, but is significantly lower than pathogenic TSC variant; assayed in human & mouse in vitro systems/non-pathogenic PubMed: Hoogeveen-Westerveld, 2011 - - In vitro (cloned) - - - - - - - - - - - - - - - - - - - - - - -
-/. 22 c.2476C>A r.(?) p.(Leu826Met) Hamartin binding domain - Unknown - benign g.2124321C>A g.2074320C>A - - TSC2_000132 - unpublished - rs45517238 Germline - - - - - DNA SEQ Blood - TSC - unpublished proband has TSC1 5'UTR variant c.-7C>T and 2 TSC2 missense variants (de novo TSC2 c.2713C>T and TSC2 c.2476C>A); parents not tested for TSC1 c.-7C>T and TSC2 c.2476C>A ? - - - - - - - 1 Rosemary Ekong
+/. 22 c.2476C>A r.(?) p.(Leu826Met) Hamartin binding domain - Unknown - pathogenic g.2124321C>A g.2074320C>A Leu825Met - TSC2_000132 reported as disease-causing PubMed: Beauchamp, 1998 - - Germline - - - - - DNA SSCA Blood - TSC S19-01 PubMed: Beauchamp, 1998 - ? - - - - - - - 1 Rosemary Ekong
-/. 22 c.2476C>A r.(?) p.(Leu826Met) Hamartin binding domain - Unknown - benign g.2124321C>A g.2074320C>A - - TSC2_000132 conservative change; reported that patient had splice change found in TSC2 intron 4 (variant not unspecified) originally Kwiatkowski database - - Germline - - - - - DNA ? Blood - TSC - originally Kwiatkowski database - ? - - - - - - - 1 Rosemary Ekong
-?/. 22 c.2476C>A r.(?) p.(Leu826Met) Hamartin binding domain - Paternal (confirmed) - likely benign g.2124321C>A g.2074320C>A - - TSC2_000132 found with TSC2 missense c.2714G>A PubMed: Sancak, 2005, PubMed: Nellist, 2005, PubMed: Jansen, 2006, PubMed: Hoogeveen-Westerveld, 2011 - - Germline - - - - - DNA DGGE, DHPLC, SSCA Blood - TSC Family B PubMed: Sancak, 2005, PubMed: Nellist, 2005, PubMed: Jansen, 2006, PubMed: Hoogeveen-Westerveld, 2011 definite TSC in mild cases; 3/4 family members examined and 3/3 have TSC2 c.2714G>A (p.Arg905Gln); 2/3 with TSC2 c.2714G>A fit definite TSC criteria; both affected children also inherited TSC2 missense c.2476C>A from unaffected father ? - Netherlands - - - - - 3 Rosemary Ekong
-?/. 22 c.2476C>A r.(?) p.(Leu826Met) Hamartin binding domain - Maternal (confirmed) - likely benign g.2124321C>A g.2074320C>A - - TSC2_000132 found with pathogenic TSC2 missense c.2713C>T unpublished - - Germline - - - - - DNA SEQ Blood - TSC - unpublished Tuberous Sclerosis clinically; patient has 2 TSC2 missense variants (c.2476C>A and c.2713C>T) M - - - - - - - 2 Rosemary Ekong
-?/. 22 c.2476C>A r.(?) p.(Leu826Met) Hamartin binding domain - Paternal (confirmed) - likely benign g.2124321C>A g.2074320C>A - - TSC2_000132 reported that variant also seen in unaffected unpublished - - Germline - - - - - DNA SEQ Blood - TSC - unpublished parental studies performed; unaffected father is a carrier of the TSC2 c.2476C>A variant M - - - - - - - 2 Rosemary Ekong
?/. 22 c.2476C>A r.(?) p.(Leu826Met) Hamartin binding domain - Unknown - VUS g.2124321C>A g.2074320C>A L826M - TSC2_000132 no DNA change reported; only predicted protein change given unpublished - - Germline - - - - - DNA SEQ Blood - TSC - unpublished patient has seizures M - - - - - - - 1 Rosemary Ekong
-/. 22 c.2476C>A r.(?) p.(Leu826Met) Hamartin binding domain - Unknown - benign g.2124321C>A g.2074320C>A - - TSC2_000132 - unpublished - - Germline - - - - - DNA SEQ Blood - TSC - unpublished ASK NICOLA IF BOTH PARENTS TESTED AS CONTRADICTORY REMARKS - RECHECK ALL TEXT IN EVERY WINDOW; 2 TS affected children but only one of the affected children and one or both??? parents and a sibling??? tested for TSC2 c.1372C>T; both parents reported as healthy and TSC2 c.1372C>T absent in both???; reported that possible germline mosaicism in one of the parents???; one of the parents and a sibling have TSC2 c.2476C>A ? - - - - - - - 1 Rosemary Ekong
-/. 22 c.2476C>A r.(?) p.(Leu826Met) Hamartin binding domain - Paternal (confirmed) - benign g.2124321C>A g.2074320C>A - - TSC2_000132 found with TSC2 nonsense c.4129C>T unpublished - - Germline - - - - - DNA DHPLC, SEQ Blood - TSC - unpublished proband has TSC2 nonsense c.4129C>T and TSC2 missense c.2476C>A; TSC2 c.4129C>T is absent in both parents, but one of the parents has TSC2 c.2476C>A M - - - - - - - 2 Rosemary Ekong
-/. 22 c.2476C>A r.(?) p.(Leu826Met) - - Unknown - likely benign g.2124321C>A - exon 21 - TSC2_000132 found with TSC2 missense c.2296G>A unpublished - - Germline ? - - - - DNA DHPLC, SEQ Blood Diagnostic testing TSC - unpublished patient has two missense variants - TSC2 c.2296G>A and TSC2 c.2476C>A; no other family member tested M ? - - - - - - 1 Rosemary Ekong
+?/. 22 c.2476C>A r.(?) p.(Leu826Met) - - Unknown - likely pathogenic (dominant) g.2124321C>A - exon 21 - TSC2_000132 - unpublished - - Germline ? - - - - DNA DHPLC, SEQ Blood Diagnostic testing TSC - unpublished No other family member tested F ? - - - - - - 1 Rosemary Ekong
-/- 22 c.2476C>A r.(?) p.(Leu826Met) Hamartin binding domain - Unknown - benign g.2124321C>A g.2074320C>A - - TSC2_000132 - - - rs45517238 SUMMARY record - 202/307504 alleles - - - - - - - - - - - - - - - - - - - - -
-?/. - c.2476C>A r.(?) p.(Leu826Met) - - Unknown - likely benign g.2124321C>A - TSC2(NM_000548.3):c.2476C>A (p.L826M), TSC2(NM_000548.5):c.2476C>A (p.L826M) - TSC2_000132 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
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Assessment of functional consequences - Our conclusions on the functional consequences of variants are based on the type of variant, results of in vitro functional tests (doi: 10.1002/humu.21451; doi: 10.1002/humu.22202; doi: 10.1002/humu.23963), population frequencies, output from in silico splice site prediction algorithms, and any clinical/family data available to us. We also have output from protein prediction programs in this database for comparison purposes and they are not considered in our assessment of pathogenicity. PolyPhen Predictions - Note that these results are from PolyPhen-2 and only the HumDiv classification is shown.


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