ClinVar

Description

The FBN1 c.8080C>T; p.Arg2694Ter variant (rs193922108) is reported in the literature in multiple individuals affected with Marfan syndrome (Attanasio 2008, Biggin 2004, Chen 2007, Hung 2009, Stheneur 2009). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 163461). It is found on one chromosome in the Exome Variant Server but is otherwise absent from general population databases (1000 Genomes Project and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Nonsense variants in FBN1 meet the revised Ghent nosology criteria for classification as pathogenic (Loeys 2010). Based on available information, this variant is considered to be pathogenic. References: Attanasio M et al. FBN1 mutation screening of patients with Marfan syndrome and related disorders: detection of 46 novel FBN1 mutations. Clin Genet. 2008 Jul;74(1):39-46. Biggin A et al. Detection of thirty novel FBN1 mutations in patients with Marfan syndrome or a related fibrillinopathy. Hum Mutat. 2004 Jan;23(1):99. Chen XJ et al. Two gene mutations in fibrillin 1 of Marfan syndrome. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007 Aug;24(4):440-2. Hung CC et al. Mutation spectrum of the fibrillin-1 (FBN1) gene in Taiwanese patients with Marfan syndrome. Ann Hum Genet. 2009 Nov;73(Pt 6):559-67. Loeys BL et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010 Jul;47(7):476-85. Stheneur C et al. Identification of the minimal combination of clinical features in probands for efficient mutation detection in the FBN1 gene. Eur J Hum Genet. 2009 Sep;17(9):1121-8.