Overview of all validated non-synonymous variants in the re-genotyping experiment combined with potential functional effects assessed by in silico analysis.

SNV, single nucleotide variant; chr, chromosome; NGS, next-generation sequencing; ESP, Exome Sequencing Project; MAF, minor allele frequency; np, not polymorphic; OR, odds ratio; Con, control; N, number of individuals; AA, amino acid; ESE, exonic splicing enhancer; ESS, exonic splicing silencer; NT, nucleotide.

Location on chr. 12 is according to the February 2009 Human Reference Sequence (UCSC Genome Browser). Known SNVs are recorded in the dbSNP137 database.

1

Case: SNV only in cases; Con: SNV only in controls;

2

N = 2734, variant was present in both the discovery and the replication sample; N = 800, variant was only polymorphic in the discovery sample; N = 1934, variant was only polymorphic in the replication sample

3

Long isoform is according to the RefSeq annotation NM_182767, the short isoform NM_018057

4

FASTSNP;

5

ANNOVAR, phastCons 46-way alignment.

6

ANNOVAR, phyloP alignment, restricted to non-synonymous variants:+conserved (score >0.95), − non-conserved (score <0.95)

7

SIFT (sorting intolerant from tolerant): − tolerant (score >0.05),+possibly damaging (score <0.05)

8

Panther: − unlikely functional effect (pdeleterious <0.5),+possibly damaging (pdeleterious >0.5)

9

PolyPhen2: − benign (score <0.15),+possibly damaging (score 0.15–0.85),++probably damaging (score >0.85).