ClinVar

Description

Variant summary: The FBN1 c.4057G>T (p.Gly1353Trp) variant located in the cb EGF-like #18 domain (via UMD) involves the alteration of a conserved nucleotide and 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). However, these predictions have yet to be functionally assessed. This variant is absent in 246104 control chromosomes (gnomAD). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. However, another variant affecting the same codon, c.4057G>A (p.Gly1353Arg) has been reported in at least one affected individual suggesting the codon could be important for proper FBN1 function, although Cysteines have been well-established to play a key role in FBN1 protein function. Therefore, due to lack of clinical information and/or functional studies, the variant is classified as a "Variant of Uncertain Significance - Possibly Pathogenic," until additional information becomes available.