ClinVar

Description

The p.R1530C pathogenic mutation (also known as c.4588C>T), located in coding exon 37 of the FBN1 gene, results from a C to T substitution at nucleotide position 4588. The arginine at codon 1530 is replaced by cysteine, an amino acid with highly dissimilar properties. The majority of FBN1 mutations identified to date have involved the substitution or generation of cysteine residues within cbEGF domains (Vollbrandt T et al. J Biol Chem. 2004;279(31):32924-32931). This pathogenic mutation has been identified in multiple individuals with ectopia lentis (EL); some of these individuals also met Ghent criteria while some did not (Loeys B et al. Arch Intern Med. 2001;161(20):2447-54; Biggin A et al. Hum Mutat. 2004;23(1):99; Jin C et al. Mol Vis. 2007;13:1280-4; Aragon-Martin JA et al. Hum Mutat. 2010;31(8):E1622-31; Vanem TT et al. Am J Med Genet A. 2020 02;182(2):397-408). This mutation was found to co-segregate with disease in two unrelated families (Rand-Hendriksen S et al. Am J Med Genet A. 2007;143A(17):1968-77; Mannucci L et al. Clin Chim Acta. 2020 Feb;501:154-164; Villamizar C et al. Eur J Med Genet. 2010; 53(2):80-4). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.