Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001040726 | SCV001204315 | pathogenic | Familial adenomatous polyposis 2 | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 12 of the MUTYH gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 32029870). ClinVar contains an entry for this variant (Variation ID: 839049). Studies have shown that disruption of this splice site results in skipping of exon 12, but is expected to preserve the integrity of the reading-frame (Invitae). This variant disrupts a region of the MUTYH protein in which other variant(s) (p.Leu388Pro) have been determined to be pathogenic (PMID: 16134147, 16941501, 17949294, 20848659, 23322991, 25820570). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |