ClinVar

Description

Although the c.4531_4534delTGTG pathogenic variant in the FBN1 gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon cysteine 1511, changing it to a threonine, and creating a premature stop codon at position 8 of the new reading frame, denoted p.Cys1511ThrfsX8. 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. Multiple other downstream frameshift variants in the FBN1 gene have been reported in Human Gene Mutation Database in association with Marfan syndrome (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.4531_4534delTGTG variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).