Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000234614 | SCV000286323 | uncertain significance | Primary ciliary dyskinesia | 2021-10-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 398 of the DNAH8 protein (p.Arg398Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs370751861, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with DNAH8-related conditions. ClinVar contains an entry for this variant (Variation ID: 238633). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
| Ambry Genetics | RCV003243022 | SCV003939337 | uncertain significance | Inborn genetic diseases | 2023-03-20 | criteria provided, single submitter | clinical testing | The c.1192C>T (p.R398C) alteration is located in exon 8 (coding exon 7) of the DNAH8 gene. This alteration results from a C to T substitution at nucleotide position 1192, causing the arginine (R) at amino acid position 398 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |