Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000991634 | SCV001143255 | pathogenic | not provided | 2018-11-02 | criteria provided, single submitter | clinical testing | The variant disrupts a canonical splice site, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data. |
Invitae | RCV000991634 | SCV003445766 | pathogenic | not provided | 2022-11-15 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 24702). This variant is also known as c.4087+1G>A or 4271+1G>A. Disruption of this splice site has been observed in individuals with Alport syndrome (PMID: 10094548, 31980082). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 44 of the COL4A5 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 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. For these reasons, this variant has been classified as Pathogenic. |