Table 2.

Characteristics of Rare Exome Variants

Family code: Gene	Codon	AA change	Base	Seen Before?	Poly- Phen2	Grantham Score	Phast- Cons	GERP++
A: RYR1	4234	VAL/LEU	G > T	G > C	0.994	32	1.0	3.07
B: RYR1	1056	ASP/HIS	G > C	G > A	1.0	81	0.999	2.94
G: RYR1	2627	VAL/MET	G > A	No	1.0	21	1.0	4.08
C: CACNA1S	1009	THR/LYS	C > A	No	0.998	78	0.987	5.12

Each row lists the characteristics of a novel rare variant suspected of being pathogenic. The letter to the left of the gene name indicates which family the variant was found in. All four variants have not been seen in any databases or in 5,379 UW ESP individuals. However, a different base change has been seen at the same position as the first two variants (Families A and B). The table includes scores that assess predicted protein change (PolyPhen2 and Grantham) and evolutionary conservation (PhastCons and GERP++), and highlights in bold either maximal scores (e.g., 1.0 for PhastCons and PolyPhen2) or extreme values.

Adenine = A; amino acid = AA; aspartic acid = ASP; calcium channel, voltage-dependent, L type, α1S subunit gene = CACNA1S; cytosine = C; exome sequencing project = ESP; genomic evolutionary rate profiling = GERP; guanine = G; histidine = HIS; leucine = LEU; lysine = LYS; methionine = MET; ryanodine receptor 1 gene = RYR1; threonine = THR; thymine = T; University of Washington = UW; valine = VAL.