ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1820C>T (p.Ala607Val)

gnomAD frequency: 0.00005  dbSNP: rs397515296
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000464888 SCV000515654 likely benign not provided 2019-11-13 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24728327, 26691941)
Invitae RCV001086928 SCV000544347 likely benign Tuberous sclerosis 2 2024-01-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV000561143 SCV000675490 likely benign Hereditary cancer-predisposing syndrome 2019-09-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000122208 SCV001339170 uncertain significance not specified 2020-03-26 criteria provided, single submitter clinical testing Variant summary: TSC2 c.1820C>T (p.Ala607Val) results in a non-conservative amino acid change located in the Tuberin-type domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 250358 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in TSC2 causing Tuberous Sclerosis Complex (4e-05 vs 6.9e-05), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1820C>T in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, two classify as likely benign while two classify as VUS. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab RCV001086928 SCV002039579 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000561143 SCV002531006 likely benign Hereditary cancer-predisposing syndrome 2021-11-19 criteria provided, single submitter curation
ITMI RCV000122208 SCV000086429 not provided not specified 2013-09-19 no assertion provided reference population

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