Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Johns Hopkins Genomics, |
RCV001682619 | SCV001905476 | uncertain significance | Ciliary dyskinesia, primary, 37 | 2021-08-27 | criteria provided, single submitter | clinical testing | This DNAH1 variant is absent from a large population dataset and has not been reported in ClinVar nor the literature, to our knowledge. Of three bioinformatics tools queried, two predict that the substitution would be damaging, while one predicts that it would be tolerated. The asparagine residue at this position is evolutionarily conserved across most species assessed. We consider the clinical significance of DNAH1 c.2992A>G to be uncertain at this time. |
| Labcorp Genetics |
RCV003771840 | SCV004583923 | uncertain significance | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2023-03-04 | 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. 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 DNAH1 protein function. ClinVar contains an entry for this variant (Variation ID: 1275740). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 998 of the DNAH1 protein (p.Asn998Asp). |