Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004066556 | SCV002755866 | uncertain significance | not specified | 2021-05-01 | criteria provided, single submitter | clinical testing | The p.I737V variant (also known as c.2209A>G), located in coding exon 17 of the GARS gene, results from an A to G substitution at nucleotide position 2209. The isoleucine at codon 737 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and valine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003103064 | SCV002937350 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2021-12-17 | criteria provided, single submitter | clinical testing | 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. 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This missense change has been observed in individual(s) with developmental disorder (PMID: 31785789). This variant is present in population databases (rs770378030, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 737 of the GARS protein (p.Ile737Val). |