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.

15 entries on 1 page. Showing entries 1 - 15.
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Effect     

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AscendingDNA change (cDNA)     

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-/. - c.5321G>C r.(?) p.(Ser1774Thr) - - Unknown - benign g.2138508G>C g.2088507G>C TSC2(NM_000548.3):c.5321G>C (p.S1774T), TSC2(NM_000548.5):c.5321G>C (p.S1774T) - TSC2_000891 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.5321G>C r.(?) p.(Ser1774Thr) - - Unknown - benign g.2138508G>C g.2088507G>C TSC2(NM_000548.3):c.5321G>C (p.S1774T), TSC2(NM_000548.5):c.5321G>C (p.S1774T) - TSC2_000891 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. 42 c.5321G>C - p.Ser1774Thr - - Unknown - NA g.2138508G>C g.2088507G>C - - TSC2_000891 TSC1 & TSC2 signals not significantly different from wild-type; mean T389/S6K ratio of variant not significantly different from that of wild-type TSC2, but is significantly lower than that of pathogenic TSC2 p.R611Q indicating its effectiveness at inhibiting TORC1; reported as probably neutral PubMed: Hoogeveen-Westerveld, 2013 - - In vitro (cloned) - - - - - - - - - - - - - - - - - - - - - - -
-/. 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Unknown - benign g.2138508G>C g.2088507G>C - - TSC2_000891 found with TSC1 frameshift c.1551del unpublished - - Germline - - - - - DNA DHPLC, SEQ Blood - TSC - unpublished patient has TSC1 frameshift c.1551del and TSC2 missense c.5321G>C; no other family member tested M - - - - - - - 1 Rosemary Ekong
+/. 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Unknown - pathogenic g.2138508G>C g.2088507G>C p.S1774T/p.S1751T - TSC2_000891 listed as pathogenic by Au et al (2007) but indicated that significance of missense unknown; variant found with a nonsense variant in a different case PubMed: Au, 2007, PubMed: Hoogeveen-Westerveld, 2013 - - Germline - - - - - DNA SSCA Blood - TSC TS92-002 PubMed: Au, 2007, PubMed: Hoogeveen-Westerveld, 2013 - ? - - - - - - - 1 Rosemary Ekong
-/. 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Unknown - benign g.2138508G>C g.2088507G>C - - TSC2_000891 found with TSC2 nonsense variant c.5170C>T, TSC2 intronic variants c.3610+42dup and c.2966+92_2966+94dup, TSC2 silent variants c.1543C>T and c.5118C>T, and TSC2 missense variant c.3986G>A unpublished - - Germline - - - - - DNA SEQ Blood - TSC - unpublished patient has TSC2 nonsense variant c.5170C>T, TSC2 intronic variants c.3610+42dup & c.2966+92_2966+94dup, TSC2 silent variants c.1543C>T & c.5118C>T, and TSC2 missense variants c.3986G>A & c.5321G>C ? - - - - - - - 1 Rosemary Ekong
?/. 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Maternal (confirmed) - VUS g.2138508G>C g.2088507G>C - - TSC2_000891 found with two TSC2 missense variants c.3206T>A and c.4316G>A; complete screen, MLPA kits P124 (TSC1) & P046 (TSC2) used unpublished - rs9209 Germline - - - - - DNA SEQ, MLPA Blood - TSC - unpublished patient has 3 TSC2 missense variants (TSC2 c.3206T>A, c.4316G>A and c.5321G>C); both apparently unaffected parents tested; TSC2 missense c.3206T>A absent in both parents, but the other two TSC2 missense variants (c.4316G>A and c.5321G>C) present in one parent and both absent in the other parent; referred for diagnostic TS testing F - - - - - - - 1 Rosemary Ekong
-/. 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Paternal (confirmed) - benign g.2138508G>C g.2088507G>C - - TSC2_000891 found with TSC2 c.2221-28A>G unpublished - - Germline - - - - - DNA SEQ Blood - TSC - unpublished patient has inherited TSC2 c.2221-28A>G and TSC2 c.5321G>C from the same parent ? - - - - - - - 2 Rosemary Ekong
-/. 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Paternal (confirmed) - benign g.2138508G>C g.2088507G>C - - TSC2_000891 - unpublished - - Germline - - - - - DNA DHPLC, SEQ Blood - TSC - unpublished variant is present in one parent and absent in the other parent F - - - - - - - 2 Rosemary Ekong
-/. 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Unknown - benign g.2138508G>C g.2088507G>C - - TSC2_000891 found with TSC2 silent variant c.1543C>T, TSC2 intronic variant c.3815-4G>A and TSC2 missense c.3973G>A unpublished - - Germline - - - - - DNA DHPLC, SEQ Blood - TSC - unpublished proband has TSC2 silent variant c.1543C>T, TSC2 intronic variant c.3815-4G>A and 2 TSC2 missense variants (c.3973G>A and c.5321G>C); proband has inherited TSC2 c.3815-4G>A from one parent but both parents also have TSC2 missense c.3973G>A; inheritance of TSC2 c.1543C>T and TSC2 c.5321G>C not indicated; TSC status of parents not indicated M - - - - - - - 1 Rosemary Ekong
-/. 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Unknown - benign g.2138508G>C g.2088507G>C - - TSC2_000891 found with TSC2 intronic variant c.-29-10G>C unpublished - - Germline - - - - - DNA DHPLC, SEQ Blood - TSC - unpublished patient has TSC2 missense c.5321G>C and TSC2 intronic variant c.-29-10G>C; no definite disease-causing variant found; No other family member tested F - - - - - - - 1 Rosemary Ekong
-/. 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Maternal (confirmed) - benign g.2138508G>C g.2088507G>C - - TSC2_000891 - unpublished - - Germline - - - - - DNA DHPLC, SEQ Blood - TSC - unpublished proband has TSC2 missense c.5321G>C and TSC2 silent variant c.1543C>T; both variants are present in one of the parents and absent in the other parent M - - - - - - - 2 Rosemary Ekong
-/. 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Unknown - likely benign g.2138508G>C - exon 41 - TSC2_000891 found with TSC2 exons 2-9 deletion, TSC1 silent c.1977G>A, TSC2 c.1258-32dup, TSC2 silent c.4908C>T and TSC2 missense c.4316G>A unpublished - - Germline ? - - - - DNA DHPLC, MLPA, SEQ Blood Diagnostic testing, MLPA (All exons for TSC1 and TSC2, exons 40 and 46 only for PKD1) TSC - unpublished prenatally detected cardiac rhabdomyomas on USS and brain lesions on fetal MRI; No other family member tested F ? - - - - - - 1 Rosemary Ekong
-/- 42 c.5321G>C r.(?) p.(Ser1774Thr) - - Unknown - benign g.2138508G>C g.2088507G>C - - TSC2_000891 - - - rs9209 SUMMARY record - 1330/143290 alleles, 24 homozygotes - - - - - - - - - - - - - - - - - - - - -
-/. - c.5321G>C r.(?) p.(Ser1774Thr) - - Unknown - benign g.2138508G>C - TSC2(NM_000548.3):c.5321G>C (p.S1774T), TSC2(NM_000548.5):c.5321G>C (p.S1774T) - TSC2_000891 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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