Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667128 | SCV000791529 | pathogenic | Autosomal recessive Alport syndrome | 2017-05-17 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000667128 | SCV000917261 | pathogenic | Autosomal recessive Alport syndrome | 2021-04-21 | criteria provided, single submitter | clinical testing | Variant summary: COL4A3 c.2621_2622delinsT (p.Gly874ValfsX9) 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 3.6e-05 in 280726 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in COL4A3 causing Alport Syndrome, Autosomal Recessive (3.6e-05 vs 0.0019), allowing no conclusion about variant significance. c.2621_2622delinsT has been reported in the literature in multiple individuals affected with Alport Syndrome, Autosomal Recessive, including one homozygous patient (Heidet_2001, Storey_2013, Moriniere_2014, Papazachariou_2014, Bierzynska_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000823486 | SCV000964347 | pathogenic | not provided | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly874Valfs*9) 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). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This premature translational stop signal has been observed in individual(s) with Alport syndrome (PMID: 11134255, 24052634, 24854265, 25514610, 28117080). This variant is also known as 2621delGAinsT. ClinVar contains an entry for this variant (Variation ID: 551951). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV000823486 | SCV002017458 | pathogenic | not provided | 2021-06-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000823486 | SCV002540341 | pathogenic | not provided | 2022-06-20 | criteria provided, single submitter | clinical testing | Identified as a single heterozygous variant in a patient with Alport syndrome in published literature, however, also identified as heterozygous in an unaffected adult sibling (Heidet et al., 2001); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 24854265, 24052634, 25514610, 28117080, 11134255) |
| Fulgent Genetics, |
RCV002493091 | SCV002801572 | pathogenic | Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria | 2022-02-16 | criteria provided, single submitter | clinical testing |