ClinVar Miner

Submissions for variant NM_000178.4(GSS):c.1054G>A (p.Ala352Thr)

gnomAD frequency: 0.00021  dbSNP: rs143974068
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000805849 SCV000945822 uncertain significance Inherited glutathione synthetase deficiency 2022-08-31 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 352 of the GSS protein (p.Ala352Thr). This variant is present in population databases (rs143974068, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with GSS-related conditions. ClinVar contains an entry for this variant (Variation ID: 650657). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811493 SCV002050090 uncertain significance not provided 2021-07-30 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001811493 SCV002541682 uncertain significance not provided 2021-12-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV003166254 SCV003875194 likely benign Inborn genetic diseases 2023-03-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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