Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000681876 | SCV001574377 | likely pathogenic | not provided | 2020-11-22 | 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL4A5 are known to be pathogenic (PMID: 9195222, 10752524, 14514738, 24854265, 26809805). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with COL4A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 562406). This variant is present in population databases (rs760109866, ExAC 0.01%). This sequence change affects an acceptor splice site in intron 30 of the COL4A5 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Gharavi Laboratory, |
RCV000681876 | SCV000809355 | pathogenic | not provided | 2018-09-16 | no assertion criteria provided | research |