ClinVar Miner

Submissions for variant NM_017777.4(MKS1):c.1435C>T (p.Arg479Cys)

gnomAD frequency: 0.00010  dbSNP: rs769442220
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
Labcorp Genetics (formerly Invitae), Labcorp RCV002538647 SCV003519796 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-06-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 479 of the MKS1 protein (p.Arg479Cys). This variant is present in population databases (rs769442220, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with MKS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1285105). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MKS1 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001702170 SCV001930868 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001727976 SCV001975117 likely benign not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004536263 SCV004116569 uncertain significance MKS1-related disorder 2024-01-23 no assertion criteria provided clinical testing The MKS1 c.1435C>T variant is predicted to result in the amino acid substitution p.Arg479Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0055% of alleles in individuals of European (Non-Finnish) descent in gnomAD. 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.