Submissions for variant NM_000548.5(TSC2):c.710C>T (p.Pro237Leu)

gnomAD frequency: 0.00007  dbSNP: rs139060277

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000190052	SCV000243727	likely benign	not specified	2016-11-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000227699	SCV000285471	likely benign	Tuberous sclerosis 2	2024-01-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001026051	SCV001188358	likely benign	Hereditary cancer-predisposing syndrome	2021-11-19	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.
Genome-Nilou Lab	RCV000227699	SCV002041255	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001026051	SCV002534097	likely benign	Hereditary cancer-predisposing syndrome	2021-04-13	criteria provided, single submitter	curation
Color Diagnostics, LLC DBA Color Health	RCV000227699	SCV004360850	uncertain significance	Tuberous sclerosis 2	2023-03-22	criteria provided, single submitter	clinical testing	This missense variant replaces proline with leucine at codon 237 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with tuberous sclerosis complex in the literature. This variant has been identified in 11/281704 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Myriad Genetics, Inc.	RCV000227699	SCV005404727	likely benign	Tuberous sclerosis 2	2024-08-06	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
PreventionGenetics, part of Exact Sciences	RCV004537600	SCV004727700	likely benign	TSC2-related disorder	2020-12-16	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).