NM_000138.5(FBN1):c.1390C>T (p.Arg464Cys) NM_00138 c.1390C>T is a missense variant in FBN1 predicted to cause a substitution of an arginine by cysteine at amino acid 464 (p.Arg464Cys). This variant has been found in two probands including one with bilateral ectopia lentis (EL) and thoracic aortic aneurysm and dissection (TAAD), and one with isolated EL (PP4, PS4_supporting; Invitae & UZG internal data, ClinVar Variation ID: 549013). The variant segregates with features of Marfan syndrome in at least two affected family members (PP1; Invitae internal data). This variant is present in gnomAD v2.1.1 (1/34578 [0.003%] Latino/Admixed American alleles; https://gnomad.broadinstitute.org/). This variant introduces a novel cysteine residue which may impede the normal formation of critical disulfide bridges (PM1). Computational prediction tools and conservation analysis are unclear about the predicted impact of this variant on the protein’s structure or function (PP3). The constraint z-score for missense variants affecting FBN1 is 5.06 (PP2). In summary, this variant meets criteria to be classified as likely pathogenic for Marfan syndrome based o the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: PM1, PS4_supporting, PP1, PP2, PP4.