Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000178163 | SCV000230170 | uncertain significance | not provided | 2014-11-23 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000548783 | SCV000651666 | pathogenic | Charcot-Marie-Tooth disease axonal type 2O | 2022-11-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg251 amino acid residue in DYNC1H1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30122514). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt DYNC1H1 protein function. ClinVar contains an entry for this variant (Variation ID: 197195). This missense change has been observed in individuals with autosomal dominant hereditary motor neuropathy (PMID: 26392352; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 251 of the DYNC1H1 protein (p.Arg251His). |
| Ambry Genetics | RCV000623418 | SCV000742400 | uncertain significance | Inborn genetic diseases | 2017-04-18 | criteria provided, single submitter | clinical testing | |
| Kariminejad - |
RCV001836743 | SCV000992237 | pathogenic | Peripheral neuropathy | 2021-07-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000178163 | SCV001769846 | pathogenic | not provided | 2020-10-30 | criteria provided, single submitter | clinical testing | Reported as likely pathogenic in an individual with hereditary motor neuropathy (HMN); however phenotypic details and segregation data were not provided (Antoniadi et al., 2015); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26392352, 30122514) |
| Mendelics | RCV002247590 | SCV002516315 | likely pathogenic | Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| CHU Sainte- |
RCV002247590 | SCV003761476 | pathogenic | Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures | 2022-03-24 | criteria provided, single submitter | clinical testing | |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV000548783 | SCV003807943 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2O | 2022-09-02 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4 strong, PM2 moderated, PM5 moderated, PP2 supporting |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV000548783 | SCV003932314 | pathogenic | Charcot-Marie-Tooth disease axonal type 2O | 2023-02-10 | criteria provided, single submitter | clinical testing | PS2, PS4_Moderate, PM2, PP2, PP3 |