Submissions for variant NM_000138.5(FBN1):c.1179_1180dup (p.Val394fs)

dbSNP: rs886041751

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000303658	SCV000330497	pathogenic	not provided	2016-09-09	criteria provided, single submitter	clinical testing	A frameshift variant that is pathogenic was identified in the FBN1 gene. Although the c.1179_1180dupGG variant has not been reported to our knowledge, this variant was found to have occurred de novo in one individual who underwent genetic testing for Marfan/TAAD at GeneDx; maternity and paternity were not confirmed. This variant causes a shift in reading frame starting at codon Valine 394, changing it to a Glycine, and creating a premature stop codon at position 2 of the new reading frame, denoted p.Val394GlyfsX2. 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 frameshift variants in the FBN1 gene have been reported in HGMD in association with Marfan syndrome (Stenson et al., 2014). Furthermore, the c.1179_1180dupGG 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.1179_1180dupGG in the FBN1 gene is interpreted as a pathogenic variant.