Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000672416 | SCV000797519 | likely pathogenic | Autosomal recessive Alport syndrome | 2018-01-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003558516 | SCV004293998 | likely pathogenic | not provided | 2023-04-12 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Alport syndrome (PMID: 16338941). It has also been observed to segregate with disease in related individuals. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 556413). This variant is present in population databases (rs768003309, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 792 of the COL4A4 protein (p.Gly792Arg). |