Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000671970 | SCV000797017 | pathogenic | Autosomal recessive Alport syndrome | 2018-01-09 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000671970 | SCV001442629 | pathogenic | Autosomal recessive Alport syndrome | 2020-10-12 | criteria provided, single submitter | clinical testing | Variant summary: COL4A3 c.4420_4424delCTTTT (p.Leu1474CysfsX34) 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. The variant was absent in 249424 control chromosomes (gnomAD). c.4420_4424delCTTTT has been reported in the literature in individuals affected with Alport Syndrome, Autosomal Recessive (Mochizuki_1994, Moriniere_2014). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV001381660 | SCV001580149 | pathogenic | not provided | 2023-11-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu1474Cysfs*34) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal dominant and autosomal recessive Alport syndrome (PMID: 7987301, 7987396). This variant is also known as a 5bp CTTTT deletion. ClinVar contains an entry for this variant (Variation ID: 556032). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000671970 | SCV000039322 | pathogenic | Autosomal recessive Alport syndrome | 1997-01-01 | no assertion criteria provided | literature only |