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

gnomAD frequency: 0.00004  dbSNP: rs761181064

Total submissions: 11

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
Labcorp Genetics (formerly Invitae), Labcorp	RCV000457441	SCV000544509	benign	Tuberous sclerosis 2	2025-01-20	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
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001545216	SCV005622736	uncertain significance	not provided	2024-07-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004537798	SCV004713140	likely benign	TSC2-related disorder	2024-02-02	no assertion criteria provided	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).