Submissions for variant NM_002103.5(GYS1):c.2043C>T (p.Ala681=)

gnomAD frequency: 0.00023  dbSNP: rs142265031

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000323667	SCV000483765	likely benign	Neuroferritinopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000359703	SCV000483766	likely benign	Hereditary hyperferritinemia with congenital cataracts	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000417882	SCV000532444	likely benign	not specified	2016-10-18	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.
Invitae	RCV000963024	SCV001110150	benign	Glycogen storage disease due to muscle and heart glycogen synthase deficiency	2024-01-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000963024	SCV001293771	uncertain significance	Glycogen storage disease due to muscle and heart glycogen synthase deficiency	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV003409562	SCV004142157	likely benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	GYS1: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003950317	SCV004765838	likely benign	GYS1-related condition	2020-02-20	criteria provided, single submitter	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).