Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001040367 | SCV001203937 | uncertain significance | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 425 of the DNAH1 protein (p.Arg425His). This variant is present in population databases (rs200951874, gnomAD 0.05%). 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: 838756). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Johns Hopkins Genomics, |
RCV001683729 | SCV001905477 | uncertain significance | Ciliary dyskinesia, primary, 37 | 2021-08-27 | criteria provided, single submitter | clinical testing | This DNAH1 variant (rs200951874) is rare (<0.1%) in a large population dataset (gnomAD: 64/277342 total alleles; 0.023%; no homozygotes) and has been reported in ClinVar (Variation ID: 838756). It has not been reported in the literature, to our knowledge. Of three bioinformatics tools queried, one predicts that the substitution would be damaging, while two predict that it would be tolerated. The arginine residue at this position is evolutionarily conserved across most species assessed, however a histidine is present in three species. We consider the clinical significance of DNAH1 c.1274G>A to be uncertain at this time. |
| Fulgent Genetics, |
RCV001040367 | SCV002812289 | uncertain significance | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2021-07-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004907673 | SCV005578096 | uncertain significance | not specified | 2024-09-26 | criteria provided, single submitter | clinical testing | The c.1274G>A (p.R425H) alteration is located in exon 8 (coding exon 7) of the DNAH1 gene. This alteration results from a G to A substitution at nucleotide position 1274, causing the arginine (R) at amino acid position 425 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |