Submissions for variant NM_001204.7(BMPR2):c.354T>G (p.Cys118Trp)

dbSNP: rs137852743

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001851760	SCV002231540	pathogenic	Primary pulmonary hypertension	2022-12-23	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 118 of the BMPR2 protein (p.Cys118Trp). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BMPR2 function (PMID: 12045205, 25688877). 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: 8799). This missense change has been observed in individuals with pulmonary hypertension (PMID: 10973254, 31727138). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency).
OMIM	RCV000009344	SCV000029562	pathogenic	Pulmonary hypertension, primary, 1	2000-09-01	no assertion criteria provided	literature only
Rare Disease Genomics Group, St George's University of London	RCV000009344	SCV000576046	pathogenic	Pulmonary hypertension, primary, 1		no assertion criteria provided	literature only
Wendy Chung Laboratory, Columbia University Medical Center	RCV001823865	SCV002073581	not provided	Pulmonary arterial hypertension; Idiopathic and/or familial pulmonary arterial hypertension		no assertion provided	literature only