Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000035167 | SCV000058809 | likely pathogenic | Marfan syndrome | 2008-03-01 | criteria provided, single submitter | clinical testing | |
Petrovsky National Research Centre of Surgery, |
RCV000035167 | SCV000987212 | pathogenic | Marfan syndrome | 2019-08-30 | criteria provided, single submitter | clinical testing | The intronic c.3337+1G>A variant was reported in one Chinese patient with aortic disease and was tested positive for a pathogenic mutation (PMID: 27611364). The variant is absent from large population studies (ExAC no frequency). ClinVar has an entry for this variant (Variation ID: 42331). There are known 3 other variants at this position: c.3337+1G>T, c.3337+1G>C, c.3337+1delG; two reported on the ClinVar (Variation ID: 527150, 574182) and one was studied in relation with MFS (PMID: 16220557). The c.3337+1G position is canonical splice site donor, all above reports on alteration of this nucleotide position show disruption of normal RNA splicing. Based on this evidences the c.3337+1G>A variant is classified as Pathogenic. |
Centre of Medical Genetics, |
RCV000035167 | SCV002025573 | likely pathogenic | Marfan syndrome | 2021-03-01 | criteria provided, single submitter | research | PM2, PS7, PP4 |
Invitae | RCV003764664 | SCV004570989 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-06-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 42331). Disruption of this splice site has been observed in individuals with clinical features of FBN1-related conditions (PMID: 16220557, 24793577, 33174221). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 27 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). |