Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000546083 | SCV000660221 | uncertain significance | Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 | 2017-07-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 654 of the DNAH1 protein (p.Arg654Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs755225053, ExAC 0.04%). This variant has not been reported in the literature in individuals with DNAH1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |