Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000315289 | SCV000330142 | pathogenic | not provided | 2016-01-07 | criteria provided, single submitter | clinical testing | Although the c.6380-2 A>C variant in the FBN1 gene has not been reported as a pathogenic variant or as a benign variant to our knowledge, it destroys the canonical splice acceptor site in intron 52 and is predicted to cause abnormal gene splicing. This variant is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Multiple other downstream splice site variants in the FBN1 gene have been reported in HGMD in association with Marfan syndrome (Stenson et al., 2014). Furthermore, the c.6380-2 A>C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, c.6380-2 A>C in the FBN1 gene is interpreted as a pathogenic variant. |
Centre of Medical Genetics, |
RCV002245989 | SCV002025387 | likely pathogenic | Marfan syndrome | 2021-03-01 | criteria provided, single submitter | research | PM2, PS7, PP1, PP4 |