. 2012 Dec 7;91(6):1135–1143. doi: 10.1016/j.ajhg.2012.10.009

Table 1.

Summary of the Pathogenic TMEM5 (NM_014254.1) and ISPD (NM_001101426.3) Mutations Detected in This Study

Family Number, Number of Sibs	Consanguinity	Gene	Zygosity	Nucleotide Variant	Amino Acid Alteration	Exon(s) Affected	Type of Mutation	Panther Prediction p_deleterious	Align GVGD Class	PolyPhen-2	SIFT
F1, 4 fetuses	yes	TMEM5	homozygous	c.795 del G	p.Arg266Glyfs^∗8	exon 5	frameshift	NA	NA	NA	NA
F7, 2 fetuses	no	TMEM5	homozygous	c.1016A>G	p.Tyr339Cys	exon 6	missense	0.82	C65	probably damaging	affected protein (0.00)
F8, 1 fetus	no	TMEM5	heterozygous	c. 1019_1020del insTT	p.Arg340Leu	exon 6	missense	0.57	C65	probably damaging	affected protein (0.00)
				c.1064_1091del	p.Asp355Valfs^∗33	exon 6	nonsense	NA	NA	NA	NA
F9, 1 fetus	no	TMEM5	heterozygous	c.1016A>G	p.Tyr339Cys	exon 6	missense	0.82	C65	probably damaging	affected protein (0.00)
				c.1064_1091del	p.Asp355Valfs^∗33	exon 6	frameshift	NA	NA	NA	NA
F10, 1 fetus	?	TMEM5	homozygous	c.279 delA	p.Gly94Glufs^∗33	exon 2	frameshift	NA	NA	NA	NA
F2, 3 fetuses	no	ISPD	heterozygous	c.638T>G	p.Met213Arg	exon 3	missense	0.67	C65	probably damaging	affected protein (0.03)
			heterozygous	deletion	deletion	exons 3 to 6 at least	gene deletion	NA	NA	NA	NA
F3, 2 fetuses	yes	ISPD	homozygous	c.466G>A	p.Asp156Asn	exon2	Missense	0.64	C15	probably damaging	affected protein (0.00)
F4, 1 fetus	no	ISPD	heterozygous	c.713C>T	p.Thr238Ile	exon4	Missense	0.22	C65	probably damaging	affected protein (0.01)
				c.256A>T	p.Arg86^∗	exon1	Nonsense	NA	NA	NA	NA
F5, 1 fetus	no	ISPD	heterozygous	c.257+2T>G	^∗	exon1	Splicing defect	NA	NA	NA	NA
				c.773C>A	p.Ser258	exon4	Nonsense	NA	NA	NA	NA
F6, 1 fetus	no	ISPD	heterozygous	c.676T>C	p.Tyr226His	exon3	Missense	0.45	C65	probably damaging	tolerated (0.43)
				deletion	deletion	Ex4 to ex6	Gene deletion	NA	NA	NA	NA

Panther: the probability that a given variant will cause a deleterious effect is estimated by p_deleterious such that a subPSEC score (substitution position-specific evolutionary conservation score based on an alignment of evolutionarily related proteins) of −3 corresponds to a p_deleterious value of 0.5. Phenotype prediction for Align GVGD class C65 corresponds to "most likely interferes with function." PolyPhen-2 extracts various sequences and structure-based features of the substitution site and feeds them into a probabilistic classifier. For the SIFT score, the amino acid substitution is predicted to be harmful if the score is ≤0.05 and is predicted to be tolerated if the score is >0.05. NA = not applicable.