Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001240298 | SCV001413230 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-04-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 388 of the GARS protein (p.Arg388Gly). This variant is present in population databases (rs759277467, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with GARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 965772). 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. 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. |
| Ambry Genetics | RCV004034646 | SCV002756150 | uncertain significance | not specified | 2020-09-22 | criteria provided, single submitter | clinical testing | The p.R388G variant (also known as c.1162C>G), located in coding exon 9 of the GARS gene, results from a C to G substitution at nucleotide position 1162. The arginine at codon 388 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |