Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667489 | SCV000791946 | likely pathogenic | Autosomal recessive Alport syndrome | 2017-05-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001066963 | SCV001231989 | pathogenic | not provided | 2023-05-23 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with autosomal recessive Alport syndrome (PMID: 15954103, 18436078, 30881523). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This sequence change creates a premature translational stop signal (p.Arg1516*) 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). This variant is present in population databases (rs759873621, gnomAD 0.0009%). ClinVar contains an entry for this variant (Variation ID: 552261). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| MGZ Medical Genetics Center | RCV000667489 | SCV002580597 | pathogenic | Autosomal recessive Alport syndrome | 2022-01-17 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002477488 | SCV002787746 | pathogenic | Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria | 2022-04-21 | criteria provided, single submitter | clinical testing | |
| Sydney Genome Diagnostics, |
RCV001328056 | SCV001449243 | pathogenic | Alport syndrome | 2018-08-28 | no assertion criteria provided | clinical testing | This patient is also heterozygous for a known pathogenic variant, c.4546C>T, in exon 49 of the COL4A3 gene. This variant creates a premature stop codon (p.Arg1516*), and may result in a null allele due to nonsense-mediated mRNA decay. This variant is considered to be pathogenic, and has been previously reported in patients with autosomal recessive Alport syndrome in the literature (Nagel et al 2005 Hum Mutat 26:60; Cook et al 2008 Am J Kidney Dis 51:e25-e28). This variant is considered to be pathogenic |