ClinVar

Description

The p.C130R pathogenic mutation (also known as c.388T>C), located in coding exon 4 of the BMPR1A gene, results from a T to C substitution at nucleotide position 388. The cysteine at codon 130 is replaced by arginine, an amino acid with highly dissimilar properties.In one study, p.C130R was detected in an individual with familial juvenilepolyposis. Themissensemutation targeted acysteineresidue in a highly conservedectodomainof theTGFβreceptor family, and this domain was known to be involved in disulfide bridge 6. Thus, authors concluded that p.C130R was very likely to result in conformational changes with functional consequences (Friedlet al. Hum Genet 2002 Jul;111(1): 108-11; Kirsch et al. NatStructBiol2000 Jun; 7(6): 492-6). In another study, this mutation was detected in a juvenilepolyposispatient and was considered pathogenic due to its location in thecysteine-richregion of the extracellular domain. There were multiple other mutations found in this region indicating hotspot (Howe et al. J Med Genet 2004 Jul; 41(7): 484-91). Based on protein sequence alignment, this amino acid position is highly conserved. In addition, this alteration is predicted to be probably damaging and deleterious byPolyphenand SIFT insilicoanalyses, respectively. Based on the majority of available evidence to date, p.C130R is classified as a pathogenic mutation.