Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000516503 | SCV000612957 | pathogenic | not provided | 2015-09-28 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV001536127 | SCV001752846 | likely pathogenic | Autosomal recessive Alport syndrome; Benign familial hematuria | 2021-06-30 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003409732 | SCV004113017 | likely pathogenic | COL4A4-related condition | 2023-06-13 | criteria provided, single submitter | clinical testing | The COL4A4 c.1118G>A variant is predicted to result in the amino acid substitution p.Gly373Glu. This variant was with a COL4A4 nonsense variant in an individual with Alport syndrome (Patient 26, Supplementary Table 1, Morinière et al 2014. PubMed ID: 24854265). The Gly373Glu variant affects a Gly residue of the conserved triple helical domain (residues 65 – 1459) of the COL4A4 protein (uniprot.org). The majority of pathogenic variants in COL4A4 substitute a glycine residue to a bulkier amino acid in the triple-helical domain (Hudson et al. 1993. PubMed ID: 8253711; https://www.ncbi.nlm.nih.gov/books/NBK1207/).This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-227963496-C-T). This variant is interpreted as likely pathogenic. |
Invitae | RCV000516503 | SCV004294004 | uncertain significance | not provided | 2022-11-28 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 447179). This missense change has been observed in individual(s) with clinical features of autosomal recessive Alport syndrome (PMID: 24854265). This variant is present in population databases (rs755649235, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 373 of the COL4A4 protein (p.Gly373Glu). 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. |
Counsyl | RCV000665733 | SCV000789900 | likely pathogenic | Autosomal recessive Alport syndrome | 2017-03-22 | no assertion criteria provided | clinical testing |