ClinVar

Description

p.Ser1550Cys (AGC>TGC): c.4648 A>T in exon 38 of the FBN1 gene (NM_000138.4)A variant of unknown significance has been identified in the FBN1 gene. The S1550C variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The S1550C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S1550C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is well conserved across species. The S1550C results in gain of Cysteine residue, which may impact disulfide bonding. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, mutations in nearby residues have not been reported in association with Marfan syndrome or FBN1-related disorder, indicating this region of the protein may tolerate change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in TAAD panel(s).