Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000669331 | SCV000794075 | uncertain significance | Autosomal recessive Alport syndrome | 2017-09-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001861775 | SCV002288671 | likely pathogenic | not provided | 2022-12-02 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1683 of the COL4A4 protein (p.Cys1683Tyr). This missense change has been observed in individuals with clinical features of autosomal dominant Alport syndrome (PMID: 26809805; Invitae). 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) 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 COL4A4 protein function. ClinVar contains an entry for this variant (Variation ID: 553809). |
Gene |
RCV001861775 | SCV003932980 | uncertain significance | not provided | 2023-06-13 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26809805, 36100708) |