Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000533473 | SCV000658889 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2022-09-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 6, but is expected to preserve the integrity of the reading-frame (PMID: 32597575). ClinVar contains an entry for this variant (Variation ID: 213795). Disruption of this splice site has been observed in individuals with SMAD3-related conditions (PMID: 32597575). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 of the SMAD3 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. |