ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.853A>T (p.Ile285Phe) (rs776026574)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000440933 SCV000535927 uncertain significance not provided 2017-01-06 criteria provided, single submitter clinical testing The I285F variant in the MARS gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I285F variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I285F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret I285F as a variant of uncertain significance.
Invitae RCV001218323 SCV001390198 uncertain significance Interstitial lung and liver disease; Charcot-Marie-Tooth disease, axonal, type 2u 2019-06-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with phenylalanine at codon 285 of the MARS protein (p.Ile285Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is present in population databases (rs776026574, ExAC 0.004%). This variant has not been reported in the literature in individuals with MARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 392628). 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: "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.

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