Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gharavi Laboratory, |
RCV000681935 | SCV000809419 | likely pathogenic | not provided | 2018-09-16 | criteria provided, single submitter | research | |
| Centogene AG - |
RCV001251195 | SCV001426586 | pathogenic | Autosomal recessive Alport syndrome | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV000681935 | SCV002231560 | pathogenic | not provided | 2022-03-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 336 of the COL4A3 protein (p.Gly336Cys). This missense change has been observed in individuals with autosomal dominant Alport syndrome (PMID: 24033287, 28632965, 32860008). For these reasons, this variant has been classified as 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) performed at Invitae indicates that this missense variant is expected to disrupt COL4A3 protein function. ClinVar contains an entry for this variant (Variation ID: 562453). |
| Fulgent Genetics, |
RCV002499210 | SCV002797280 | pathogenic | Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria | 2022-03-29 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV004788113 | SCV005398508 | pathogenic | Alport syndrome | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative, caused by missense variants mostly glycine substitutions that affect the conformation of the protein, and loss of function, caused by either protein truncating and missense variants, are known mechanisms of disease in this gene and are associated with Alport syndrome and benign familial hematuria (PMID: 12028435). (I) 0108 - This gene is associated with both recessive (Alport syndrome 2 (MIM#203780)) and dominant disease (Alport syndrome 3 (MIM#104200) and benign familial hematuria (MIM#141200)) (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0601 - Variant is located in the well-established functional collagen triple helix domain, affecting glycine of the G-X-Y repeats (PDB). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals with Alport or hematuria (ClinVar, Global LOVD, PMID: 24033287, 28632965). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |