ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5308C>T (p.Pro1770Ser)

gnomAD frequency: 0.00004  dbSNP: rs761181064
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000340010 SCV000395682 uncertain significance Tuberous sclerosis syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000457441 SCV000544509 benign Tuberous sclerosis 2 2023-12-11 criteria provided, single submitter clinical testing
GeneDx RCV001545216 SCV001764498 likely benign not provided 2020-09-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function
Genome-Nilou Lab RCV000457441 SCV002040281 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002255364 SCV002534050 likely benign Hereditary cancer-predisposing syndrome 2022-03-09 criteria provided, single submitter curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002298569 SCV002598662 uncertain significance not specified 2022-09-30 criteria provided, single submitter clinical testing Variant summary: TSC2 c.5308C>T (p.Pro1770Ser) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 281580 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5308C>T in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters have assessed the variant since 2014 without evidence for independent evaluation: one classified the variant as uncertain significance, three as likely benign, and one as benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002255364 SCV002647218 likely benign Hereditary cancer-predisposing syndrome 2023-01-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Revvity Omics, Revvity RCV000457441 SCV003821607 uncertain significance Tuberous sclerosis 2 2023-11-22 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001545216 SCV004033438 uncertain significance not provided 2023-07-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004537798 SCV004713140 likely benign TSC2-related disorder 2024-02-02 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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