Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000669678 | SCV000794454 | pathogenic | Autosomal recessive Alport syndrome | 2017-09-26 | criteria provided, single submitter | clinical testing | |
| Institute Of Human Genetics Munich, |
RCV000669678 | SCV001149718 | pathogenic | Autosomal recessive Alport syndrome | 2019-06-07 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001861779 | SCV002141522 | pathogenic | not provided | 2022-10-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 554110). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal dominant and recessive Alport syndrome (PMID: 12028435). This variant is present in population databases (rs766900945, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg1037*) in the COL4A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL4A3 are known to be pathogenic (PMID: 8956999, 24854265, 26809805, 27281700). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000669678 | SCV002500295 | pathogenic | Autosomal recessive Alport syndrome | 2022-03-10 | criteria provided, single submitter | clinical testing | Variant summary: COL4A3 c.3109C>T (p.Arg1037X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 249484 control chromosomes. c.3109C>T has been reported in the literature as a compound heterozygous genotype in individuals affected with Alport Syndrome, Autosomal Recessive (example, Longo_2002, Moriniere_2014). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000735743 | SCV000863898 | pathogenic | Autosomal dominant Alport syndrome | 2018-06-14 | no assertion criteria provided | clinical testing |