ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.1852C>T (p.Arg618Cys) (rs587777718)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478608 SCV000568853 uncertain significance not provided 2017-03-03 criteria provided, single submitter clinical testing The R618C variant in the MARS gene has been reported previously in the heterozygous state in a male individual and his maternal uncle, both of whom had late-adult onset of peripheral axonal neuropathy classified as Charcot-Marie-Tooth disease type 2U (CMT2U); however, this variant was also observed in the individual's unaffected mother (Gonzalez et al., 2013). This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R618C 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, and occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function, and functional studies demonstrated that the R618C variant did not rescue growth of yeast deficient in an ortholog of MARS (Gonzales et al., 2013). However, additional studies are needed to validate the functional effect of this variant in vivo. We interpret R618C as a variant of uncertain significance.
Molecular Genetics Laboratory,London Health Sciences Centre RCV000192267 SCV001336525 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
OMIM RCV000144083 SCV000189158 pathogenic Charcot-Marie-Tooth disease, axonal, type 2u 2013-11-01 no assertion criteria provided literature only
GeneReviews RCV000192267 SCV000239915 pathogenic Charcot-Marie-Tooth disease 2015-04-30 no assertion criteria provided literature only
Hadassah Hebrew University Medical Center RCV000677354 SCV000692464 likely pathogenic Interstitial lung and liver disease no assertion criteria provided clinical testing

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