ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.2053G>A (p.Val685Ile) (rs558631075)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000526373 SCV000655631 uncertain significance Interstitial lung and liver disease; Charcot-Marie-Tooth disease, axonal, type 2u 2017-08-02 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 685 of the MARS protein (p.Val685Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MARS-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002141 SCV001159996 uncertain significance not specified 2018-10-09 criteria provided, single submitter clinical testing The MARS c.2053G>A; p.Val685Ile variant (rs558631075), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 475418). This variant is found in the general population with an overall allele frequency of 0.001% (4/277,206 alleles) in the Genome Aggregation Database. The valine at codon 685 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Val685Ile variant is uncertain at this time.

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