Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001208002 | SCV001379372 | uncertain significance | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2023-03-18 | 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. This variant disrupts the p.Arg1702 amino acid residue in DNAH1. Other variant(s) that disrupt this residue have been observed in individuals with DNAH1-related conditions (PMID: 31676830), which suggests that this may be a clinically significant amino acid residue. 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 DNAH1 protein function. ClinVar contains an entry for this variant (Variation ID: 938725). This missense change has been observed in individual(s) with severe sperm motility disorders (PMID: 34089056). This variant is present in population databases (rs753810465, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1702 of the DNAH1 protein (p.Arg1702Gln). |