Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002238452 | SCV002508536 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2021-03-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with GARS-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with alanine at codon 460 of the GARS protein (p.Gly460Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Gene |
RCV003126204 | SCV003803537 | uncertain significance | not provided | 2022-08-12 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26503042, 26138142, 25168514) |