ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.370T>C (p.Cys124Arg)

dbSNP: rs199476087
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165949 SCV000216705 pathogenic Hereditary cancer-predisposing syndrome 2020-09-24 criteria provided, single submitter clinical testing The p.C124R pathogenic mutation (also known as c.370T>C), located in coding exon 4 of the BMPR1A gene, results from a T to C substitution at nucleotide position 370. The cysteine at codon 124 is replaced by arginine, an amino acid with highly dissimilar properties. This alteration has been identified in individuals meeting diagnostic criteria for juvenile polyposis syndrome (Zhou XP et al. Am J Hum Genet. 2001 Oct;69(4):704-11; Ambry internal data) and co-segregated with disease in one family tested in our laboratory. This amino acid position is highly conserved on sequence alignment. The p.C124R variant results in the loss of the Cys residue and alters the folding of the BMPR1A extracellular domain (Ambry internal structural analysis). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
GeneDx RCV001836704 SCV002097427 likely pathogenic not provided 2022-02-07 criteria provided, single submitter clinical testing Identified in a patients with a personal or family history consistent with pathogenic variants in this gene referred for genetic testing at GeneDx and in published literature (Zhou 2001); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12136244, 11536076, 12761718, 15235019, 26986070, 30884445, 29745898, 10881198, 22799562, 23433720)
Baylor Genetics RCV003473059 SCV004212663 likely pathogenic Polyposis syndrome, hereditary mixed, 2 2022-05-04 criteria provided, single submitter clinical testing
OMIM RCV001797979 SCV000028926 pathogenic Juvenile polyposis syndrome 2001-10-01 no assertion criteria provided literature only

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