ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.1673C>A (p.Pro558His)

gnomAD frequency: 0.00003  dbSNP: rs771808261
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000652558 SCV000774428 uncertain significance Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2023-01-12 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 542172). This variant has not been reported in the literature in individuals affected with MARS-related conditions. This variant is present in population databases (rs771808261, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 558 of the MARS protein (p.Pro558His). 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. 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 disruptive.
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173444 SCV001336533 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
GeneDx RCV001756101 SCV001985270 uncertain significance not provided 2019-08-15 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV003420144 SCV004117917 uncertain significance MARS1-related disorder 2022-10-17 criteria provided, single submitter clinical testing The MARS1 c.1673C>A variant is predicted to result in the amino acid substitution p.Pro558His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-57906056-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.