Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000461393 | SCV000553784 | uncertain significance | Charcot-Marie-Tooth disease, type 2 | 2019-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 340 of the AARS protein (p.Asn340Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs140135726, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with distal myopathy (PMID: 25783436). ClinVar contains an entry for this variant (Variation ID: 412288). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |
Molecular Genetics Laboratory, |
RCV000999701 | SCV001156487 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |