Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489618 | SCV000577290 | pathogenic | not provided | 2017-04-05 | criteria provided, single submitter | clinical testing | Although the c.3258delT variant in the FBN1 gene has not been reported to our knowledge, this deletioncauses a shift in reading frame starting at codon Cysteine 1086, changing it to a Tryptophan, and creating apremature stop codon at position 2 of the new reading frame, denoted p.Cys1086TrpfsX2. This deletion isexpected to result in either an abnormal, truncated protein product or loss of protein from this allele throughnonsense-mediated mRNA decay. Other frameshift variants in the FBN1 gene have been reported inHGMD in association with Marfan syndrome (Stenson P et al., 2014). Furthermore, the c.3258delTvariant was not observed in approximately 6,500 individuals of European and African American ancestryin the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, c.3258delT in the FBN1 gene is interpreted as a pathogenic variant. |