Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000668884 | SCV000793558 | likely pathogenic | Autosomal recessive Alport syndrome | 2017-08-18 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000668884 | SCV001361061 | pathogenic | Autosomal recessive Alport syndrome | 2022-02-16 | criteria provided, single submitter | clinical testing | Variant summary: COL4A3 c.663_664delAG (p.Arg221SerfsX5) 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 1.6e-05 in 249216 control chromosomes. c.663_664delAG has been reported in the literature in at least one individual affected with Alport Syndrome, Autosomal Recessive (Storey_2013). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV001330982 | SCV001522861 | pathogenic | Autosomal dominant Alport syndrome | 2019-01-18 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Invitae | RCV001384278 | SCV001583718 | pathogenic | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg221Serfs*5) 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 (no rsID available, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with autosomal recessive Alport syndrome (PMID: 24052634). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 553434). For these reasons, this variant has been classified as Pathogenic. |