Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Biology Laboratory, |
RCV001029796 | SCV001425008 | likely pathogenic | Autosomal dominant Alport syndrome | 2020-02-01 | criteria provided, single submitter | research | |
| Center of Genomic medicine, |
RCV001029796 | SCV001739310 | likely pathogenic | Autosomal dominant Alport syndrome | 2021-02-09 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV004789365 | SCV005399671 | uncertain significance | Alport syndrome | 2024-10-09 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. 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) (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 (3 heterozygotes, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated C-terminal tandem repeated domain in type 4 procollagen (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been classified as likely pathogenic and as a VUS in ClinVar. This variant has also been observed in a father and child with hearing loss and no sign of altered kidney function (PMID: 34440452), and in an individual with familial FSGS and hearing loss; however, they also harboured two in trans COL4A4 variants, one of which was a stopgain variant (PMID: 33532864). (SP) 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 |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV001029796 | SCV001192575 | uncertain significance | Autosomal dominant Alport syndrome | 2019-06-03 | no assertion criteria provided | clinical testing |