Table 2.

Pathogenicity assessment of the novel missense mutations in the RS1 gene

Nucleotide change	Amino acid change	Folding energy value⁶ (assessment)	Polyphen2 HumDIV¹⁰ (cutoff = 0.85)	GERP++¹¹ (cutoff = 2)	REVEL¹² (cutoff = 0.5)^a	M-CAP¹³ (cutoff = 0.025)	CADD¹⁴ phred (cutoff = 15)^b	PROVEAN¹⁵ (cutoff = −2.5)	SIFT¹⁵ (cutoff = 0.05)	Mutation Accessor¹⁶ (cutoff = 1.9)	FATHMM¹⁷ (cutoff = −1.5)
c.35T>C	p.Leu12Pro	NA	0.984	5.69	0.701	0.782	25.100	−1.120	0.003	2.095	−5.160
c.175T>G	p.Cys59Gly	0.04 (weak)	0.999	5.15	0.868	0.844	23.900	−2.850	0.000	2.610	−5.010
c.218C>T	p.Ser73Leu	0.22 (weak)	0.953	5.43	0.825	0.896	27.200	−4.460	0.002	3.925	−5.630
c.326G>C	p.Gly109Ala	1 (severe)	1.000	5.43	0.740	0.921	28.000	−0.860	0.233	0.780	−4.810
c.404G>A	p.Gly135Glu	1 (severe)	0.953	4.91	0.985	0.943	27.100	−5.540	0.001	3.515	−5.610
c.417G>T	p.Gln139His	1 (severe)	0.996	2.14	0.920	0.949	23.800	−4.830	0.001	4.435	−5.600
c.625C>A	p.Arg209Ser	0.74 (moderate)	1.000	5.63	0.770	0.909	25.700	−0.200	0.044	1.695	−5.220

Underlined values are indicated as “pathogenic” according to the cutoff values (refs. ^10–17)

NA not applicable

^a75.4% of disease mutations but 10.9% of neutral variants

^b≤1% percentile highest scores