Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV001535999 | SCV001752674 | likely pathogenic | Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria | 2021-06-30 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002568227 | SCV003222279 | likely pathogenic | not provided | 2024-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1228 of the COL4A3 protein (p.Gly1228Val). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of autosomal dominant COL4A3-related conditions (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1179129). 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 with a positive predictive value of 95%. 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. |
Ambry Genetics | RCV003346606 | SCV004076511 | likely pathogenic | Inborn genetic diseases | 2023-08-16 | criteria provided, single submitter | clinical testing | The c.3683G>T (p.G1228V) alteration is located in exon 42 (coding exon 42) of the COL4A3 gene. This alteration results from a G to T substitution at nucleotide position 3683, causing the glycine (G) at amino acid position 1228 to be replaced by a valine (V). Based on data from gnomAD, the T allele has an overall frequency of 0.001% (1/186352) total alleles studied. The highest observed frequency was 0.007% (1/13976) of East Asian alleles. This amino acid position is highly conserved in available vertebrate species. The p.G1228 amino acid is located within the triple-helical domain of the collagen alpha-3(IV) chain, and this alteration affects one of the highly conserved glycine residues in the Gly-X-Y motif that make up this domain (Ramshaw, 1998). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |