ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.228G>T (p.Glu76Asp) (rs369313141)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756320 SCV000884091 uncertain significance not provided 2018-01-22 criteria provided, single submitter clinical testing The MARS c.228G>T; p.Glu76Asp variant (rs369313141), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.002% (identified on 5 out of 246,264 chromosomes). The glutamic acid at position 76 is moderately conserved, considering 12 species, and computational analyses of the effects of the p.Glu76Asp variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Glu76Asp variant cannot be determined with certainty.
Invitae RCV001069411 SCV001234575 uncertain significance Interstitial lung and liver disease; Charcot-Marie-Tooth disease, axonal, type 2u 2019-03-08 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 76 of the MARS protein (p.Glu76Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs369313141, ExAC 0.01%). This variant has not been reported in the literature in individuals with MARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 618205). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.

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