ClinVar Miner

Submissions for variant NM_002047.4(GARS1):c.843G>A (p.Met281Ile)

gnomAD frequency: 0.00001  dbSNP: rs545669679
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Total submissions: 3
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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.

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