Submissions for variant NM_000548.5(TSC2):c.1831C>G (p.Arg611Gly)

dbSNP: rs45469298

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001388105	SCV001588964	pathogenic	Tuberous sclerosis 2	2020-03-24	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg611 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9463313, 17304050, 11741832, 21309039). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces arginine with glycine at codon 611 of the TSC2 protein (p.Arg611Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individual(s) with tuberous sclerosis complex (PMID: 21520333, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 49177). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000042433	SCV005848171	pathogenic	Tuberous sclerosis syndrome	2025-02-18	criteria provided, single submitter	clinical testing	ACMG criteria used: PS2, PS4_Supporting, PM2, PM5, PP3
Tuberous sclerosis database (TSC2)	RCV000042433	SCV000066224	not provided	Tuberous sclerosis syndrome		no assertion provided	curation