Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000471841 | SCV000546403 | uncertain significance | Primary ciliary dyskinesia | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2198 of the DNAH8 protein (p.Met2198Ile). This variant is present in population databases (rs765618018, gnomAD 0.006%). 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: 407306). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNAH8 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. |
Ambry Genetics | RCV003298482 | SCV003998312 | uncertain significance | Inborn genetic diseases | 2023-05-16 | criteria provided, single submitter | clinical testing | The c.6594G>A (p.M2198I) alteration is located in exon 47 (coding exon 46) of the DNAH8 gene. This alteration results from a G to A substitution at nucleotide position 6594, causing the methionine (M) at amino acid position 2198 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |