Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000991619 | SCV001143232 | likely pathogenic | not provided | 2018-10-29 | criteria provided, single submitter | clinical testing | The variant disrupts a glycine residue in the canonical Gly-X-Y repeats of the triple helix domain, which are required for stability and structure of this protein. Therefore it is expected to severely affect the function of the protein. Not found in the total gnomAD dataset, and the data is high quality (0/248928 chr). |
| Invitae | RCV000991619 | SCV002254958 | uncertain significance | not provided | 2021-07-21 | criteria provided, single submitter | clinical testing | 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) performed at Invitae indicates that this missense variant is expected to disrupt COL4A4 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. ClinVar contains an entry for this variant (Variation ID: 804580). This variant has not been reported in the literature in individuals affected with COL4A4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 819 of the COL4A4 protein (p.Gly819Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. |