Submissions for variant NM_001204.7(BMPR2):c.1039T>C (p.Cys347Arg)

dbSNP: rs1085307290

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001360167	SCV001556070	pathogenic	Primary pulmonary hypertension	2022-11-29	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 347 of the BMPR2 protein (p.Cys347Arg). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys347 amino acid residue in BMPR2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12045205, 16429395, 26645265). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BMPR2 protein function. ClinVar contains an entry for this variant (Variation ID: 425865). This missense change has been observed in individuals with pulmonary arterial hypertension (PMID: 16429395, 32581362). This variant is not present in population databases (gnomAD no frequency).
Rare Disease Genomics Group, St George's University of London	RCV000488554	SCV000576155	pathogenic	Pulmonary hypertension, primary, 1		no assertion criteria provided	literature only
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003706	SCV001162149	pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research