Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV003326900 | SCV004033355 | uncertain significance | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | DYNC1H1: PM2, PS2:Supporting |
Prevention |
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 |
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). |