Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000550341 | SCV000660270 | uncertain significance | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1985 of the DNAH1 protein (p.Met1985Val). This variant is present in population databases (rs376873184, gnomAD 0.03%). 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: 478469). 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 with a positive 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. |
| Ambry Genetics | RCV002527963 | SCV003730850 | uncertain significance | Inborn genetic diseases | 2022-01-19 | criteria provided, single submitter | clinical testing | The c.5953A>G (p.M1985V) alteration is located in exon 38 (coding exon 37) of the DNAH1 gene. This alteration results from a A to G substitution at nucleotide position 5953, causing the methionine (M) at amino acid position 1985 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |