ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.5921C>A (p.Pro1974Gln) (rs199615641)

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
Integrated Genetics/Laboratory Corporation of America RCV000735881 SCV000864094 uncertain significance not specified 2018-08-06 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.5915C>A (p.Pro1972Gln, alternative name c.5921C>A) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00017 in 275940 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in ALMS1 causing Cardiomyopathy (0.00017 vs 0.0022), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.5915C>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000735881 SCV000967347 uncertain significance not specified 2018-09-10 criteria provided, single submitter clinical testing The p.Pro1974Gln variant in ALMS1 has not been previously reported in individual s with hearing loss or Alstrom syndrome but it has been identified in 5/10104 As hkenazi Jewish chromosomes and 41/125726 European chromosomes by the Genome Aggr egation Database (gnomAD, http://gnomad.broadinstitute.org). Computational predi ction tools and conservation analysis suggest that the p.Pro1974Gln variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Pro1974Gln va riant is uncertain. ACMG/AMP Criteria applied: BP4, PM2_Supporting.
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV001172524 SCV001335577 likely benign Monogenic diabetes 2017-10-06 criteria provided, single submitter research ACMG criteria: BP4 (7 predictors), BP1 (missense variant when truncating is disease causing)=likely benign

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.