Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000704032 | SCV000832965 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-07-07 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs777170136, gnomAD 0.002%). 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. 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) performed at Invitae indicates that this missense variant is expected to disrupt AARS protein function. ClinVar contains an entry for this variant (Variation ID: 580481). This variant has not been reported in the literature in individuals affected with AARS-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 99 of the AARS protein (p.Glu99Lys). |
| Ambry Genetics | RCV002462054 | SCV002755330 | uncertain significance | Inborn genetic diseases | 2022-09-14 | criteria provided, single submitter | clinical testing | The p.E99K variant (also known as c.295G>A), located in coding exon 2 of the AARS gene, results from a G to A substitution at nucleotide position 295. The glutamic acid at codon 99 is replaced by lysine, an amino acid with 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. |