Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003767931 | SCV004609429 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 22 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 individuals with clinical features of Marfan syndrome (PMID: 33414558; Invitae). ClinVar contains an entry for this variant (Variation ID: 549102). 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. |
Center for Medical Genetics Ghent, |
RCV000663569 | SCV000786880 | likely pathogenic | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |