ClinVar Miner

Submissions for variant NM_002103.5(GYS1):c.803A>T (p.His268Leu)

gnomAD frequency: 0.00002  dbSNP: rs769630976
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001134176 SCV001293906 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001134176 SCV002148054 uncertain significance Glycogen storage disease due to muscle and heart glycogen synthase deficiency 2021-05-19 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with GYS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 894180). This variant is present in population databases (rs769630976, ExAC 0.01%). This sequence change replaces histidine with leucine at codon 268 of the GYS1 protein (p.His268Leu). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and leucine.

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