Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000655831 | SCV000777762 | uncertain significance | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2023-05-27 | 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 expected to disrupt DNAH1 protein function. ClinVar contains an entry for this variant (Variation ID: 544634). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. This variant is present in population databases (rs371787188, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1783 of the DNAH1 protein (p.Arg1783Leu). |
| Ambry Genetics | RCV003343981 | SCV004065972 | uncertain significance | Inborn genetic diseases | 2023-06-16 | criteria provided, single submitter | clinical testing | The c.5348G>T (p.R1783L) alteration is located in exon 34 (coding exon 33) of the DNAH1 gene. This alteration results from a G to T substitution at nucleotide position 5348, causing the arginine (R) at amino acid position 1783 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV003424262 | SCV004118457 | uncertain significance | DNAH1-related condition | 2023-03-31 | criteria provided, single submitter | clinical testing | The DNAH1 c.5348G>T variant is predicted to result in the amino acid substitution p.Arg1783Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-52398865-G-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |