Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002310873 | SCV000319322 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2014-09-22 | criteria provided, single submitter | clinical testing | The c.3209-1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide upstream from coding exon 26 of the FBN1 gene. Since alterations that disrupt the canonical splice acceptor site are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
| Labcorp Genetics |
RCV003765555 | SCV004593731 | likely pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-02-16 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 26 of the FBN1 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 FBN1 are known to be pathogenic (PMID: 17657824, 19293843). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with FBN1-related conditions (PMID: 17657824, 29848614). ClinVar contains an entry for this variant (Variation ID: 263860). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |