Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000653859 | SCV000775749 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-06-30 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 543182). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (Invitae). This variant is present in population databases (rs781585447, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 657 of the GARS protein (p.Arg657Cys). 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 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 | RCV004025918 | SCV002755188 | uncertain significance | not specified | 2020-03-03 | criteria provided, single submitter | clinical testing | The p.R657C variant (also known as c.1969C>T), located in coding exon 16 of the GARS gene, results from a C to T substitution at nucleotide position 1969. The arginine at codon 657 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |