ClinVar

Description

Variant summary: The FBN1 c.5898_5912delAGATGGGAGGACCTG (p.Asp1967_Cys1971del) variant located in an EGF-like domain causes an in-frame deletion, involving a Cysteine. "The sulfhydryl group of cysteine is unique in its ability to participate in disulfide covalent cross-linkage. In fact, two thirds of fibrillin cysteine residues exist in the half-cystinyl form, suggesting their participation in intramolecular disulfide linkage. The cysteine residues in the EGF-like motif may also be necessary for intermolecular interactions with other fibrillin molecules or with other proteins (Dietz_1992)." The Cys 1971 is involved in disulfide bond with Cys1958, therefore, deletion of cysteine in this domain disrupt disulfide binding, effecting secondary or tertiary structure or possibly impairing fibrillin interactions. This variant is absent in 121066 control chromosomes (ExAC). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as a "Variant of Uncertain Significance - Possibly Pathogenic."