ClinVar Miner

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

gnomAD frequency: 0.00004  dbSNP: 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 Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 685 of the MARS protein (p.Val685Ile). This variant is present in population databases (rs558631075, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 475418). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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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