Case | Sex | Age at diagnosis | Age at death | mPAP (mm Hg) | PVRi (Woods units) | Treatment | Variant(s) | Mutation type | MAF gnomAD v2.1.1 (controls) | CADD score h38v1.6 | SIFT | PolyPhen2 (HumVar) | Previously-reported for PAH? | ACMG class |
F1 II.1 | M | 2.5 years | 4 years | nk | Sildenafil and diuretics | c.2563G>A (p.Val855Met) rs1489314131 | Missense (homozygous) | absent | 26.5 | D | D | Barozzi 201914 | LP | |
F1 II.2 | M | 2.5 years | 8 years | 40 | Sildenafil, bosentan, intravenous epoprostenol and lung transplantation | c.2563G>A (p.Val855Met) rs1489314131 | Missense (homozygous) | absent | 26.5 | D | D | Barozzi 201914 | LP | |
F2 II.2 | M | 5 months | 11 months | 34* | 11.8 | Oxygen, diuretics, sildenafil, bosentan and intravenous treprostinil | c.2549dupT (p.Met850Ilefs13) rs1560082927 | Frameshift | 9.21e-6 (no homo) | 33 | D | D | Zhu 20194 | P |
c.2227C>T (p.Arg743Cys) | Missense | absent | 32 | D | D | Zhu 20194 | LP | |||||||
F2 II.4 | F | 7 days | 17 months | 51* | 11.8 | Oxygen, diuretics, sildenafil, bosentan and subcutaneous treprostinil | c.2549dupT (p.Met850Ilefs13) rs1560082927 | Frameshift | 9.21e-6 (no homo) | 33 | D | D | Zhu 20194 | P |
c.2227C>T (p.Arg743Cys) | Missense | absent | 32 | D | D | Zhu 20194 | LP | |||||||
F3 I.1 | F | 22 months | alive | 59* | 34.3 | Sildenafil, bosentan, treprostinil and digoxin | c.3079dupT (p.Trp1027Leufs9) rs746602775 | Frameshift | absent | absent | --- | -- | no | P |
c.3685G>T (p.Glu1229) rs200914446 | Nonsense | absent | 26.4 | --- | --- | no | P |
Variant nomenclature according to transcript NM_001367549.1.
Deleteriousness predictions: CADD score>20: deleterious; SIFT or PolyPhen score=D: protein damaging.
ACMG class: LP: likely pathogenic; P: pathogenic.
*Non-responder to inhaled nitric oxide or oxygen. F1 II.1 and II.2 were not tested.
CADD, Combined Annotation Dependent Depletion; mPAP, mean pulmonary artery pressure; nk, not known; PAH, pulmonary arterial hypertension; PVRi, pulmonary vascular resistance index; SIFT, Sorting Intolerant from Tolerant.