ClinVar

Description

Although the c.1965_1966delTG likely pathogenic variant in the FLNC gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon alanine 656, changing it to a proline, and creating a premature stop codon at position 8 of the new reading frame, denoted p.Ala656ProfsX8. This likely 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 downstream frameshift variants in the FLNC gene have been reported in Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.1965_1966delTG variant has not been observed in large population cohorts (Lek et al., 2016).In summary, c.1965_1966delTG in the FLNC gene is interpreted as a likely pathogenic variant.