ClinVar Miner

Submissions for variant NM_170784.3(MKKS):c.871G>A (p.Val291Ile)

gnomAD frequency: 0.00002  dbSNP: rs910468710
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001244292 SCV001417501 uncertain significance Bardet-Biedl syndrome; McKusick-Kaufman syndrome 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 291 of the MKKS protein (p.Val291Ile). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MKKS-related conditions. ClinVar contains an entry for this variant (Variation ID: 969036). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MKKS protein function. This variant disrupts the p.Val291 amino acid residue in MKKS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2896767, 22353939). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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.