Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Wong Mito Lab, |
RCV000714943 | SCV000845713 | likely pathogenic | Combined oxidative phosphorylation defect type 14 | 2018-06-13 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001092144 | SCV001248521 | pathogenic | not provided | 2019-09-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000714943 | SCV001582544 | pathogenic | Combined oxidative phosphorylation defect type 14 | 2022-03-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects FARS2 function (PMID: 28419689). 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 FARS2 protein function. ClinVar contains an entry for this variant (Variation ID: 587672). This variant is also known as Gly273Ser. This missense change has been observed in individuals with FARS2-related conditions (PMID: 28419689, 30177229). It has also been observed to segregate with disease in related individuals. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 309 of the FARS2 protein (p.Gly309Ser). |
3billion | RCV000714943 | SCV003842096 | likely pathogenic | Combined oxidative phosphorylation defect type 14 | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.89; 3Cnet: 0.65). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000587672). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |