NM_00138 c.5443G>A is a missense variant in FBN1 predicted to cause a substitution of a Glycine by Serine at amino acid 1815 (p.Gly1815Ser). This variant has been reported 3 times in ClinVar: once as likely pathogenic and twice as a variant of uncertain significance (Variation ID: 200064). This variant has been reported in the literature in 2 probands. It was identified in the homozygous state in an individual with autism spectrum disorder, global developmental delays, arachnodactyly, and dysmorphic features (PMID: 32655337); of note, homozygous variants of uncertain significance were identified in two other genes in this individual, and all 3 homozygous variants were found to segregate with disease in a similarly affected sibling. It was identified in another individual with sudden unexplained death in epilepsy, for which an autopsy did not identify any cardiac abnormalities (PMID: 27930701). This variant was also identified in an internal proband with thoracic aortic dissection and a systemic score >7 however, a pathogenic nonsense variant in FBN1 was also identified in this individual (BP2) and was considered to explain the phenotype . This variant has been identified in 0.0033% of individuals of South Asian origin in gnomAD v2.1.1. (https://gnomad.broadinstitute.org/). Computational prediction tools and conservation analysis are unclear on the predicted impact on the protein. The constraint z-score for missense variants affecting FBN1 is 5.06 however due to the presence of one benign argument PP2 cannot be used . In summary, this variant meets the criteria to be classified as uncertain significance for Marfan syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: BP2