ClinVar Miner

Submissions for variant NM_002103.5(GYS1):c.1243G>A (p.Asp415Asn)

gnomAD frequency: 0.00009  dbSNP: rs573897595
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000996957 SCV001151974 uncertain significance not provided 2019-04-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001040760 SCV001204349 uncertain significance Glycogen storage disease due to muscle and heart glycogen synthase deficiency 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 415 of the GYS1 protein (p.Asp415Asn). This variant is present in population databases (rs573897595, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with GYS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 808611). 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 GYS1 protein function. 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.
Illumina Laboratory Services, Illumina RCV001040760 SCV001290822 uncertain significance Glycogen storage disease due to muscle and heart glycogen synthase deficiency 2018-01-13 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.
Ambry Genetics RCV002549955 SCV003739484 uncertain significance Inborn genetic diseases 2021-08-20 criteria provided, single submitter clinical testing The c.1243G>A (p.D415N) alteration is located in exon 10 (coding exon 10) of the GYS1 gene. This alteration results from a G to A substitution at nucleotide position 1243, causing the aspartic acid (D) at amino acid position 415 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV001040760 SCV003835093 uncertain significance Glycogen storage disease due to muscle and heart glycogen synthase deficiency 2021-09-09 criteria provided, single submitter clinical testing

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