Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001209460 | SCV001380897 | uncertain significance | Combined oxidative phosphorylation defect type 27 | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with cysteine at codon 108 of the CARS2 protein (p.Phe108Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine. This variant is present in population databases (rs201577762, ExAC 0.07%). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Pediatric Department, |
RCV003232231 | SCV002760197 | uncertain significance | See cases | criteria provided, single submitter | clinical testing | This variant was observed in compound heterozygosity with variant (c.1036C>T) |