Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000536044 | SCV000660232 | uncertain significance | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 859 of the DNAH1 protein (p.Asn859Ser). This variant is present in population databases (rs200428788, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 478431). 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 with a negative predictive value of 80%. 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. |
| Prevention |
RCV003945346 | SCV004766054 | uncertain significance | DNAH1-related condition | 2023-11-15 | criteria provided, single submitter | clinical testing | The DNAH1 c.2576A>G variant is predicted to result in the amino acid substitution p.Asn859Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.070% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-52384054-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |