Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523629 | SCV000619353 | uncertain significance | not provided | 2017-07-25 | criteria provided, single submitter | clinical testing | The M55V variant in the GARS gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The M55V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on currently available evidence, we interpret M55V as a variant of uncertain significance. |
| Labcorp Genetics |
RCV001347311 | SCV001541564 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-08-29 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with clinical features of GARS-related conditions (Invitae). 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. 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 GARS protein function. ClinVar contains an entry for this variant (Variation ID: 450741). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 55 of the GARS protein (p.Met55Val). |