Table 2. Missense changes found in the coding region of the BMPR2, ACVRL1 and KCNA5 genes and their classification according to three different computer algorithms (PolyPhen-2, Pmut and SIFT).

CLASSIFICATION MISSENSE VARIATIONS FOUND IN THE CODING REGION OF GENES
Gene	Nucleotide change	Amino-acid change	Times founded	PolyPhen-2	Pmut	Sift	Score
BMPR2 (Exon 2)	c.190A>C	p.(S64G)	1	Benign	Neutral	Tolerated	0
BMPR2 (Exon 2)	c.229A>T	p.(I77L)	1	Benign	Neutral	Damaging	1
BMPR2 (Exon 3)	c.251G>T	p.(C84F)	2	Probably damaging	Neutral	Damaging	2
BMPR2 (Exon 3)	c.259C>T	p.(H87Y)	1	Benign	Neutral	Damaging	1
BMPR2 (Exon 3)	c.275A>T	p.(Q92L)	1	Benign	Pathologic	Damaging	2
BMPR2 (Exon 4)	c.484G>C	p.(A162P)	1	Probably damaging	Neutral	Damaging	2
BMPR2 (Exon 6)	c.790G>A	p.(D264N)	1	Possibly damaging	Neutral	Damaging	2
BMPR2 (Exon 8)	c.1021G>A	p.(V341M)	3	Possibly damaging	Neutral	Damaging	2
BMPR2 (Exon 12)	c.2324G>A	p.(S775N)	2	Benign	Neutral	Tolerated	0
ACVRL1 (Exon 2)	c.24A>T	P(.K8N)	1	Benign	Neutral	Tolerated	0
ACVRL1 (Exon 3)	c.176A>T	p.(E59V)	1	Benign	Neutral	Tolerated	0
ACVRL1 (Exon 4)	c.476A>T	p.(E159V)	1	Benign	Neutral	Tolerated	0
ACVRL1 (Exon 6)	c.673A>T	p.(S225C)	1	Probably Damaging	Pathological	Damaging	3
ACVRL1 (Exon 8)	c.1186A>G	p.(T396A)	8	Benign	Neutral	Tolerated	0
KCNA5 (Exon 1)	c.125T>A	p.(L42H)	1	Benign	Neutral	Tolerated	0
KCNA5 (Exon 1)	c.253C>A	p.(L85M)	1	Benign	Neutral	Tolerated	0
KCNA5 (Exon 1)	c.340A>C	p.(T114P)	1	Benign	Neutral	Tolerated	0
KCNA5 (Exon 1)	c.385C>G	p.(L119V)	2	Benign	Neutral	Damaging	1
KCNA5 (Exon 1)	c.509C>G	p.(P170R)	1	Probably Damaging	Pathological	Damaging	3
KCNA5 (Exon 1)	c.551G>C	p.(R184P)	1	Probably Damaging	Pathological	Damaging	3
KCNA5 (Exon 1)	c.1733G>A	p.(R577K)	1	Benign	Neutral	Tolerated	0

These results are considered damaging if the score is equal or greater than two.