Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Biology Laboratory, |
RCV000006873 | SCV001425077 | pathogenic | Asphyxiating thoracic dystrophy 3 | 2020-02-01 | criteria provided, single submitter | research | |
| 3billion | RCV000006873 | SCV002572893 | likely pathogenic | Asphyxiating thoracic dystrophy 3 | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000006500). A different missense change at the same codon (p.Met1991Lys) has been reported to be associated with DYNC2H1 -related disorder (ClinVar ID: VCV000439632 / PMID: 23456818). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Invitae | RCV003586122 | SCV004313769 | likely pathogenic | Jeune thoracic dystrophy | 2023-09-01 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Met1991 amino acid residue in DYNC2H1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23456818). 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 not expected to disrupt DYNC2H1 protein function. ClinVar contains an entry for this variant (Variation ID: 6500). This missense change has been observed in individuals with DYNC2H1-related conditions (PMID: 19442771, 33532864). 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 methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1991 of the DYNC2H1 protein (p.Met1991Leu). |
| OMIM | RCV000006873 | SCV000027069 | pathogenic | Asphyxiating thoracic dystrophy 3 | 2009-05-01 | no assertion criteria provided | literature only |