Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CHEO Genetics Diagnostic Laboratory, |
RCV001170899 | SCV001333529 | likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2018-10-26 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001170899 | SCV002706742 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2019-12-09 | criteria provided, single submitter | clinical testing | The c.1525-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 7 of the TGFBR2 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript; however, this canonical site occurs at the 3' terminus of TGFBR2, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 59 amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |