Submissions for variant NM_001079855.2(GYG2):c.584C>T (p.Thr195Met)

gnomAD frequency: 0.00068  dbSNP: rs143109649

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000839357	SCV000981256	likely benign	not provided	2018-01-09	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	RCV000839357	SCV003286019	uncertain significance	not provided	2024-10-16	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 226 of the GYG2 protein (p.Thr226Met). This variant is present in population databases (rs143109649, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with GYG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 679662). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Ambry Genetics	RCV004029218	SCV003686094	uncertain significance	not specified	2022-01-07	criteria provided, single submitter	clinical testing	The c.677C>T (p.T226M) alteration is located in exon 7 (coding exon 6) of the GYG2 gene. This alteration results from a C to T substitution at nucleotide position 677, causing the threonine (T) at amino acid position 226 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics	RCV000839357	SCV005207903	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003938188	SCV004754364	likely benign	GYG2-related disorder	2023-04-14	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).