Submissions for variant NM_000548.5(TSC2):c.3958G>A (p.Val1320Ile)

gnomAD frequency: 0.00001  dbSNP: rs767495365

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000573012	SCV000675660	likely benign	Hereditary cancer-predisposing syndrome	2021-05-17	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	RCV001722536	SCV000717503	likely benign	not provided	2019-02-19	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27930734)
Invitae	RCV000644391	SCV000766084	benign	Tuberous sclerosis 2	2023-12-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000644391	SCV002039798	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153748	SCV003843366	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003230549	SCV003929061	likely benign	not specified	2023-04-24	criteria provided, single submitter	clinical testing	Variant summary: TSC2 c.3958G>A (p.Val1320Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.7e-05 in 244812 control chromosomes in the gnomAD database, including 1 homozygote. To our knowledge, no occurrence of c.3958G>A in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters have assessed the variant since 2014: three classified the variant as likely benign and two as benign. Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV001722536	SCV004129849	likely benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	TSC2: BP4, BS2