Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000681808 | SCV002072688 | likely pathogenic | not provided | 2022-01-18 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in in-frame deletion within a critical region. Variant damages or destroys the canonical splice donor site in intron 23, and is expected to cause abnormal gene splicing; if the splice outcome is exon skip, the loss of the encoded residues in the triple helical region is expected to disrupt normal protein folding and function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24854265, 25575550) |
Eurofins- |
RCV003236588 | SCV003935098 | pathogenic | Autosomal recessive Alport syndrome | 2022-11-24 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000681808 | SCV004294016 | likely pathogenic | not provided | 2023-06-23 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: 562351). Disruption of this splice site has been observed in individual(s) with clinical features of autosomal recessive Alport syndrome and/or glomerulopathy (PMID: 24854265, 30586318). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 23 of the COL4A3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL4A3 are known to be pathogenic (PMID: 8956999, 24854265, 26809805, 27281700). |
Gharavi Laboratory, |
RCV000681808 | SCV000809279 | pathogenic | not provided | 2018-09-16 | no assertion criteria provided | research |