Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000389578 | SCV000330816 | pathogenic | not provided | 2016-09-21 | criteria provided, single submitter | clinical testing | Although the c.2598_2601dupCAAT pathogenic variant in the FBN1 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon Glycine 868, changing it to a Glutamine, and creating a premature stop codon at position 27 of the new reading frame, denoted p.Gly868GlnfsX27. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the FBN1 gene have been reported in HGMD in association with FBN1-related disorders, including Marfan syndrome (Stenson et al., 2014). Furthermore, c.2598_2601dupCAAT 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.2598_2601dupCAAT in the FBN1 gene is interpreted as a pathogenic variant. |