Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001038534 | SCV001202008 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-08-21 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant Charcot-Marie-Tooth disease (PMID: 23279345; Invitae). This variant is also known as p.Asp146Asn. ClinVar contains an entry for this variant (Variation ID: 637545). 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. Experimental studies have shown that this missense change affects GARS function (PMID: 25168514). This variant disrupts the p.Asp200 amino acid residue in GARS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26244500). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 200 of the GARS protein (p.Asp200Asn). |
Inherited Neuropathy Consortium | RCV000789775 | SCV000929159 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only | ||
Inherited Neuropathy Consortium Ii, |
RCV003447259 | SCV004174551 | uncertain significance | Neuronopathy, distal hereditary motor, type 5 | 2016-01-06 | no assertion criteria provided | literature only |