Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center For Human Genetics And Laboratory Diagnostics, |
RCV001726707 | SCV001961029 | likely pathogenic | Autosomal dominant Alport syndrome | 2021-03-25 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV004785293 | SCV005399635 | likely pathogenic | Alport syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Pathogenic. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with Alport syndrome, MONDO:0018965, COL4A3-related. Glycine changes that are part of a G-X-Y repeat in the triple helix of a collagen domain are known to have a dominant negative effect (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 haematuria MIM#141200) (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to valine. (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 glycine change within a G-X-Y motif (DECIPHER). (SP) 0710 - Other missense variants comparable to the one identified in this case have inconclusive previous evidence for pathogenicity. These variants (p.(Gly712Arg, p.(Gly712Ser)) have each been reported as a VUS (ClinVar). (I) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been reported as likely pathogenic with limited clinical information (LOVD, ClinVar), and also observed in a family with dominant Alport syndrome (PMID: 26411580). (SP) 0906 - Segregation evidence for this variant is inconclusive. This variant has segregated in two affected individuals within a single family; however, this is an insufficient number of meioses to be used as evidence for pathogenicity (PMID: 26411580). (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 |