Table 3. Candidate gene mutational screening.
6 genes (ATP2A2, CAV1, CAV2, SLC8A1, SRL, TRPM7) at 5 loci were screened for amino-acid altering variants in 298 LQTS cases and compared to >300 same-ancestry controls, presence on an exome chip array designed from exome sequencing of >12,000 multi-racial samples (number of alternate alleles shown) and in the Exome Sequencing Project (alternate allele counts per total number of individuals shown). Predicted function by Polyphen2 (BENign, POSSibly damaging or PROBably damaging) or SIFT (TOLerated, DAMaging) is also indicated. See Supplementary Material for details.
| gene | position hg19 | exon | nucleotide change | amino acid change | # cases | in controls (yes/no) | alt alleles in Exome Chip | in ESP | PolyPhen/SIFT |
|---|---|---|---|---|---|---|---|---|---|
| ATP2A2 | chr12:110,734,419 | 5 | c.340_A>G | p.Asn114Asp | 1 | no | no | no | BEN/TOL |
| ATP2A2 | chr12:110,765,553 - 110,765,554 | 8 | c.826_827insA | p.Ile276fsX281 | 1 | no | no | no | STOP |
| SLC8A1 | chr2:40,656,318 | 1 | c.1104_C>T | p.Ala368Val | 1 | no | no | 24/5379 | PROB/TOL |
| SLC8A1 | chr2:40,397,450 | 6 | c.2009_C>T | p.Pro670Leu | 1 | no | no | no | BEN/DAM |
| SLC8A1 | chr2:40,342,664 | 10 | c.2651_T>G | p.Val884Gly | 1 | no | no | no | PROB/DAM |
| SRL | chr16:4,256,990 | 2 | c.1177_G>T | p.Gly393Cys | 1 | no | no | no | PROB/DAM |
| SRL | chr16:4,256,754 | 2 | c.1409_G>A | p.Arg470Lys | 1 | no | no | no | BEN/TOL |
| SRL | chr16:4,256,384 | 7 | c.2566_C>T | p.Arg856Cys | 1 | no | no | 1/4915 | PROB/TOL |
| TRPM7 | chr15:50,955,189 | 2 | c.58_INS_A | p.Ile19fsX59 | 1 | no | no | no | STOP |
| TRPM7 | chr15:50,935,731 | 5 | c.341_A>T | p.Asp114Val | 1 | no | no | no | PROB/DAM |
| TRPM7 | chr15:50,884,537 | 26 | c.3895_A>C | p.Ser1299Arg | 1 | no | no | no | BEN/TOL |
| TRPM7 | chr15:50,884,406 | 26 | c.4026_A>T | p.Glu1342Asp | 2 | no | no | no | BEN/TOL |
| TRPM7 | chr15:50,884,280 | 26 | c.4152_A>T | p.Leu1384Phe | 1 | no | no | no | POSS/TOL |