Submissions for variant NM_000548.5(TSC2):c.4795G>A (p.Val1599Met)

gnomAD frequency: 0.00006  dbSNP: rs772687631

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001088185	SCV000285418	likely benign	Tuberous sclerosis 2	2023-12-27	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000415747	SCV000340218	uncertain significance	not provided	2016-03-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000415747	SCV000493501	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000570208	SCV000675460	likely benign	Hereditary cancer-predisposing syndrome	2018-06-28	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.
GeneDx	RCV000415747	SCV000977095	likely benign	not provided	2018-06-12	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.
Genome-Nilou Lab	RCV001088185	SCV002040222	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003417808	SCV004113180	uncertain significance	TSC2-related condition	2023-08-08	criteria provided, single submitter	clinical testing	The TSC2 c.4795G>A variant is predicted to result in the amino acid substitution p.Val1599Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2136326-G-A) and is reported in ClinVar as uncertain and likely benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/238061/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.