Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000664680 | SCV000788681 | likely pathogenic | Autosomal recessive Alport syndrome | 2017-10-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001855429 | SCV002305356 | likely pathogenic | not provided | 2021-09-10 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 COL4A3 protein function. ClinVar contains an entry for this variant (Variation ID: 550056). This missense change has been observed in individuals with autosomal recessive Alport syndrome and/or clinical features of Alport syndrome (PMID: 24854265, 25575550). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 689 of the COL4A3 protein (p.Gly689Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |