Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000655821 | SCV000777752 | uncertain significance | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2023-06-26 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs371251530, gnomAD 0.007%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1844 of the DNAH1 protein (p.Lys1844Arg). 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: 544624). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNAH1 protein function. |
| Ambry Genetics | RCV002534238 | SCV003681421 | uncertain significance | Inborn genetic diseases | 2022-06-28 | criteria provided, single submitter | clinical testing | The c.5531A>G (p.K1844R) alteration is located in exon 35 (coding exon 34) of the DNAH1 gene. This alteration results from a A to G substitution at nucleotide position 5531, causing the lysine (K) at amino acid position 1844 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |