ClinVar

Description

Identified in a patient with dilated aortic root and tall stature; however, this individual did not have a typical Marfanoid appearance or ocular symptoms, did not meet diagnostic criteria for Marfan syndrome, and segregation studies to investigate whether the variant was present in the father with mitral valve insufficiency were not performed (Rommel et al., 2002); In silico analysis supports that this missense variant does not alter protein structure/function; Although located in a calcium-binding EGF-like domain of the FBN1 gene, it does not affect a cysteine residue within this domain; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (Collod-Beroud et al., 2003); In vitro functional study suggests that variant p.V449I may affect FBN1 binding affinity; however, since experiments were conducted using FBN1 fragments rather than full-length FBN1, additional studies required (Chaudry et al., 2007); This variant is associated with the following publications: (PMID: 25652356, 24941995, 25812041, 25637381, 12402346, 17242066, 31211626)