Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000992026 | SCV001143987 | likely benign | not provided | 2018-11-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001337244 | SCV001530837 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 281 of the GARS protein (p.Met281Ile). This variant is present in population databases (rs545669679, gnomAD 0.06%). 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: 804828). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 | RCV002462249 | SCV002755884 | uncertain significance | Inborn genetic diseases | 2021-09-16 | criteria provided, single submitter | clinical testing | The p.M281I variant (also known as c.843G>A), located in coding exon 7 of the GARS gene, results from a G to A substitution at nucleotide position 843. The methionine at codon 281 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |