ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.12760G>A (p.Gly4254Arg)

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
CeGaT Center for Human Genetics Tuebingen RCV003326900 SCV004033355 uncertain significance not provided 2023-08-01 criteria provided, single submitter clinical testing DYNC1H1: PM2, PS2:Supporting
PreventionGenetics, part of Exact Sciences RCV003395752 SCV004110185 likely pathogenic DYNC1H1-related disorder 2023-04-12 criteria provided, single submitter clinical testing The DYNC1H1 c.12760G>A variant is predicted to result in the amino acid substitution p.Gly4254Arg. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although this variant has not been reported, it is expected to be pathogenic as many other de novo missense variants in DYNC1H1 have previously been reported to be pathogenic for DYNC1H1-related disorders (Human Gene Mutation Database). This variant is interpreted as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003528460 SCV004335023 uncertain significance Charcot-Marie-Tooth disease axonal type 2O 2023-06-15 criteria provided, single submitter clinical testing 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 DYNC1H1 protein function. This variant has not been reported in the literature in individuals affected with DYNC1H1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 4254 of the DYNC1H1 protein (p.Gly4254Arg).

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.