ClinVar Miner

Submissions for variant NM_006567.5(FARS2):c.667C>T (p.Arg223Cys) (rs202060864)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196357 SCV000251370 likely pathogenic not provided 2014-04-24 criteria provided, single submitter clinical testing p.Arg223Cys (CGC>TGC): c.667 C>T in exon 3 of the FARS2 gene (NM_006567.3). The R223C variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R223C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is highly conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s).
Invitae RCV000650594 SCV000772441 uncertain significance Combined oxidative phosphorylation deficiency 14 2018-07-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 223 of the FARS2 protein (p.Arg223Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs202060864, ExAC 0.2%). This variant has not been reported in the literature in individuals with FARS2-related disease. ClinVar contains an entry for this variant (Variation ID: 214330). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000650594 SCV001164195 likely pathogenic Combined oxidative phosphorylation deficiency 14 2018-04-10 criteria provided, single submitter clinical testing

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