Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000687541 | SCV000815114 | uncertain significance | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2022-08-06 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 567451). This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. This variant is present in population databases (rs201610799, gnomAD 0.04%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1370 of the DNAH1 protein (p.Glu1370Lys). |
| Prevention |
RCV003420217 | SCV004115048 | uncertain significance | DNAH1-related condition | 2023-03-14 | criteria provided, single submitter | clinical testing | The DNAH1 c.4108G>A variant is predicted to result in the amino acid substitution p.Glu1370Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.037% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-52392595-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |