One in ACVLR1 gene, but after functional analysis there were notScientific RepoRts | 6:33570 | DOI: 10.1038/srepwww.nature.com/scientificreports/Mutation c.190A > C (p.S64G) BMPR2 c.229A > T (p.I77L) BMPR2 c.251G > T (p.C84F) BMPR2 PolyPhen-2 Benign Pmut Neutral Sift Tolerated Mutation Taster ONO-4059 web Disease causing NNSplice Neutral The WT consensus sequence is not order TAPI-2 recognized Score for the aceptor site increases from 87 to 89 NetGen2 The WT consensus sequence is not recognized Score for the main donor site increases from 31 to 34 Score for the main acceptor site decreases from 33 to 27 Score for the main acceptor site decreases from 33 to 25 Neutral Score for the main donor site decrease from 94 to 77 Score for the main donor site decreases from 94 to 92 Neutral Neutral The main aceptor site is not recognized Splice View A new donor site is created Neutral HSF Human Score for donor and acceptor site decreases from 85 to 52 A new acceptor site is created The main donor site is not recognized Score for donor and acceptor site increases from 59 to 89 and from 89 to 92 The main donor site is not recognized Score for donor and acceptor site decrease from 87 to 57 and from 79 to 35 The main donor site is not recognized The main donor site is not recognized The main donor and acceptor sites are not recognized Score for main acceptor site increase from 69 to 85 ScoreBenignNeutralDamagingDisease causingProbably DamagingNeutralDamagingDisease causingNeutralc.275A > T (p.Q92L) BMPR2 c.412C > G (p.P138A) BMPR2 c.742A > G (p.R248G) BMPR2 c.790G > A (p.D264N) BMPR2 c.1021G > A (p.V341M) BMPR2 c.24A > T (p.K8N) ACVRL1 c.682G > A (p.V228I) ACVRLBenignPathologicDamagingDisease causingNeutralNeutralProbably DamagingNeutralDamagingDisease causingNeutralNeutralBenignNeutralDamagingDisease causingNeutralNeutralPossibly damaging Possibly damaging BenignNeutral Neutral NeutralDamaging Damaging ToleratedDisease causing Disease causing Disease causingNeutral Neutral Score for the main acceptor site increases from 66 to 76 NeutralNeutral The WT consensus sequence is not recognized Neutral5 4Probably DamagingNeutralDamagingDisease causingNeutralc.694T > A (p.S232T) ACVRL1 c.760G > A (p.D254N) ACVRLProbably DamagingNeutralDamagingDisease causingScore for main donor site increase from 69 to 93 Score for main donor site decrease from 69 to 48 Neutral Neutral Neutral The WT consensus sequence is not recognizedNeutral Score for main donor site increase from 65 to 75 Score for the main acceptor site increase from 35 to 37 Neutral Score for the main donor site decreases from 69 to 67 The WT consensus sequence is not recognizedThe main donor site is not The WT consensus recognized and a sequence is not new acceptor site is recognized created Neutral Neutral A new acceptor site is created A new acceptor site is created A new acceptor site is createdProbably DamagingNeutralDamagingDisease causingc.775G > A (p.V259M) Probably Damaging ENGNeutralDamaging Tolerated Tolerated DamagingPolymorphism Disease causing Polymorphism Disease causingNeutral Neutral Neutral4 4 4c.1633G > A (p.G545S) Probably Damaging Pathological ENG c.1660C > A (p.R554C) Probably Damaging Pathological ENG c.676C > A (p.P226T) KCNA5 Probably Damaging PathologicalThe WT consensus The WT consensus sequence is not sequence is not recognized recognizedTable 3. Bioinformatic assessment of the pathogenic nature of missense variations. Score: number of bioinformatic tools that evidence the pathogenic nature of the vari.One in ACVLR1 gene, but after functional analysis there were notScientific RepoRts | 6:33570 | DOI: 10.1038/srepwww.nature.com/scientificreports/Mutation c.190A > C (p.S64G) BMPR2 c.229A > T (p.I77L) BMPR2 c.251G > T (p.C84F) BMPR2 PolyPhen-2 Benign Pmut Neutral Sift Tolerated Mutation Taster Disease causing NNSplice Neutral The WT consensus sequence is not recognized Score for the aceptor site increases from 87 to 89 NetGen2 The WT consensus sequence is not recognized Score for the main donor site increases from 31 to 34 Score for the main acceptor site decreases from 33 to 27 Score for the main acceptor site decreases from 33 to 25 Neutral Score for the main donor site decrease from 94 to 77 Score for the main donor site decreases from 94 to 92 Neutral Neutral The main aceptor site is not recognized Splice View A new donor site is created Neutral HSF Human Score for donor and acceptor site decreases from 85 to 52 A new acceptor site is created The main donor site is not recognized Score for donor and acceptor site increases from 59 to 89 and from 89 to 92 The main donor site is not recognized Score for donor and acceptor site decrease from 87 to 57 and from 79 to 35 The main donor site is not recognized The main donor site is not recognized The main donor and acceptor sites are not recognized Score for main acceptor site increase from 69 to 85 ScoreBenignNeutralDamagingDisease causingProbably DamagingNeutralDamagingDisease causingNeutralc.275A > T (p.Q92L) BMPR2 c.412C > G (p.P138A) BMPR2 c.742A > G (p.R248G) BMPR2 c.790G > A (p.D264N) BMPR2 c.1021G > A (p.V341M) BMPR2 c.24A > T (p.K8N) ACVRL1 c.682G > A (p.V228I) ACVRLBenignPathologicDamagingDisease causingNeutralNeutralProbably DamagingNeutralDamagingDisease causingNeutralNeutralBenignNeutralDamagingDisease causingNeutralNeutralPossibly damaging Possibly damaging BenignNeutral Neutral NeutralDamaging Damaging ToleratedDisease causing Disease causing Disease causingNeutral Neutral Score for the main acceptor site increases from 66 to 76 NeutralNeutral The WT consensus sequence is not recognized Neutral5 4Probably DamagingNeutralDamagingDisease causingNeutralc.694T > A (p.S232T) ACVRL1 c.760G > A (p.D254N) ACVRLProbably DamagingNeutralDamagingDisease causingScore for main donor site increase from 69 to 93 Score for main donor site decrease from 69 to 48 Neutral Neutral Neutral The WT consensus sequence is not recognizedNeutral Score for main donor site increase from 65 to 75 Score for the main acceptor site increase from 35 to 37 Neutral Score for the main donor site decreases from 69 to 67 The WT consensus sequence is not recognizedThe main donor site is not The WT consensus recognized and a sequence is not new acceptor site is recognized created Neutral Neutral A new acceptor site is created A new acceptor site is created A new acceptor site is createdProbably DamagingNeutralDamagingDisease causingc.775G > A (p.V259M) Probably Damaging ENGNeutralDamaging Tolerated Tolerated DamagingPolymorphism Disease causing Polymorphism Disease causingNeutral Neutral Neutral4 4 4c.1633G > A (p.G545S) Probably Damaging Pathological ENG c.1660C > A (p.R554C) Probably Damaging Pathological ENG c.676C > A (p.P226T) KCNA5 Probably Damaging PathologicalThe WT consensus The WT consensus sequence is not sequence is not recognized recognizedTable 3. Bioinformatic assessment of the pathogenic nature of missense variations. Score: number of bioinformatic tools that evidence the pathogenic nature of the vari.
