Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000666144 | SCV000790388 | likely pathogenic | Autosomal recessive Alport syndrome | 2017-03-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001855453 | SCV002294604 | pathogenic | not provided | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1103 of the COL4A4 protein (p.Gly1103Arg). This variant is present in population databases (rs749299357, gnomAD 0.004%). This missense change has been observed in individuals with autosomal recessive Alport syndrome (PMID: 24633401, 26628290, 35369551). ClinVar contains an entry for this variant (Variation ID: 551160). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001855453 | SCV003842531 | uncertain significance | not provided | 2023-02-28 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A4 gene; This variant is associated with the following publications: (PMID: 26628290, 35369551, 35419377, 24633401) |