ClinVar Miner

Submissions for variant NM_006567.5(FARS2):c.971A>G (p.Tyr324Cys)

gnomAD frequency: 0.00048  dbSNP: rs142073519
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196488 SCV000251373 likely pathogenic not provided 2014-07-07 criteria provided, single submitter clinical testing p.Tyr324Cys (TAC>TGC): c.971 A>G in exon 5 of the FARS2 gene (NM_006567.3). The Y324C variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The Y324C 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 conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (D325Y and I329T) have been reported in association with epilepsy, infantile-onset and mitochondrial encephalopathy, supporting the functional importance of this region of the protein. 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).
Labcorp Genetics (formerly Invitae), Labcorp RCV000541945 SCV000652856 uncertain significance Combined oxidative phosphorylation defect type 14 2025-01-13 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 324 of the FARS2 protein (p.Tyr324Cys). This variant is present in population databases (rs142073519, gnomAD 0.2%). 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: 214333). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt FARS2 protein function with a positive predictive value of 95%. 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.
Baylor Genetics RCV000541945 SCV003836099 uncertain significance Combined oxidative phosphorylation defect type 14 2021-12-23 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.