Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000676729 | SCV000251000 | uncertain significance | not provided | 2021-02-25 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
| Illumina Laboratory Services, |
RCV000185551 | SCV001320276 | uncertain significance | Combined oxidative phosphorylation defect type 8 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV000676729 | SCV002214288 | uncertain significance | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 554 of the AARS2 protein (p.Arg554Cys). This variant is present in population databases (rs146924860, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with AARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 203376). 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 not expected to disrupt AARS2 protein function with a negative predictive value of 80%. 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. |
| Division of Human Genetics, |
RCV000185551 | SCV000238433 | uncertain significance | Combined oxidative phosphorylation defect type 8 | 2015-05-07 | no assertion criteria provided | research | The heterozygous variant in the AARS2 gene (c.1660C>T; p.Arg554Cys)is considered a Variant of Unknown significance. This variant has not been previously published but was seen in 98 individuals (out of 122736 alleles interrogated at this position) in the ExAC database. The amino acid position is not well conserved across species while the nucleotide position is only moderately conserved, the change is however non-conservative. |
| Mayo Clinic Laboratories, |
RCV000676729 | SCV000802529 | uncertain significance | not provided | 2016-02-25 | no assertion criteria provided | clinical testing |