ClinVar Miner

Submissions for variant NM_006567.5(FARS2):c.1220C>T (p.Thr407Met)

gnomAD frequency: 0.00006  dbSNP: rs372054960
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198201 SCV000251371 likely pathogenic not provided 2014-09-08 criteria provided, single submitter clinical testing p.Thr407Met (ACG>ATG): c.1220 C>T in exon 7 of the FARS2 gene (NM_006567.3). The T407M variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The T407M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity and size. This substitution occurs at a position that is conserved across species and 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 RCV000691495 SCV000819278 uncertain significance Combined oxidative phosphorylation defect type 14 2022-09-07 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 407 of the FARS2 protein (p.Thr407Met). This variant is present in population databases (rs372054960, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with FARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 214331). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly 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.

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