Submissions for variant NM_000548.5(TSC2):c.183A>G (p.Ile61Met)

dbSNP: rs2084961841

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001304127	SCV001493397	uncertain significance	Tuberous sclerosis 2	2020-10-01	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function. This variant has not been reported in the literature in individuals with TSC2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 61 of the TSC2 protein (p.Ile61Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine.
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV003127778	SCV003804112	likely benign	Autism spectrum disorder	2021-08-13	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003462870	SCV004206852	uncertain significance	Isolated focal cortical dysplasia type II	2023-09-05	criteria provided, single submitter	clinical testing