ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.1241G>A (p.Arg414Gln)

gnomAD frequency: 0.00001  dbSNP: rs1280661109
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173428 SCV001336516 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Invitae RCV001299882 SCV001488998 uncertain significance Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2023-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 414 of the MARS protein (p.Arg414Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 917031). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Ambry Genetics RCV004032952 SCV002755677 uncertain significance not specified 2021-07-14 criteria provided, single submitter clinical testing The p.R414Q variant (also known as c.1241G>A), located in coding exon 10 of the MARS gene, results from a G to A substitution at nucleotide position 1241. The arginine at codon 414 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.