Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003004960 | SCV003300207 | uncertain significance | Combined oxidative phosphorylation defect type 27 | 2022-08-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 503 of the CARS2 protein (p.Ala503Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CARS2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV004068466 | SCV004917944 | uncertain significance | Inborn genetic diseases | 2024-03-04 | criteria provided, single submitter | clinical testing | The c.1508C>T (p.A503V) alteration is located in exon 14 (coding exon 14) of the CARS2 gene. This alteration results from a C to T substitution at nucleotide position 1508, causing the alanine (A) at amino acid position 503 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |