Table 2.
Overview of pathogenic and likely pathogenic variants in the sudden death cohort
| Case | Age at death (years) | Sex | Circumstances of death | Symptoms before death | Autopsy finding | Gene | Chr | Starta | End | Ref/Alt | MAFb dbSNP | cDNA changea | Amino acid changea | ACMG classification | ACMG criteriac |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P1 | 26 | F | Light activity | Seizures | ACM | DSP | 6 | 7580818 | 7580818 | T/G | None | c.4395T>G | p.(Y1465*) | Likely pathogenic | PVS1.PM2 |
| P2 | 28 | M | Light activity | None | ACM | DSP | 6 | 7581692 | 7581692 | C/T | None | c.5269C>T | p.(Q1757*) | Likely pathogenic | PVS1, PM2 |
| P3 | 20 | M | Exercise | None | ACM | TMEM43 | 3 | 14183165 | 14183165 | C/T | None | c.1073C>T | p.(S358L) | Pathogenic | PS3, PS4, PM2, PP3 |
| rs63750743 | |||||||||||||||
| P4 | 37 | M | Sleep | None | ACM | PKP2 | 12 | 32955433 | 32955438 | GGGTGT/G | 1.6 × 10−5 | c.2066_2070delACACC | p.(H689Pfs*8) | Pathogenic | PVS1, PS4 |
| P5 | 29 | M | Light activity | Seizures | DCM | TNNI3 | 19 | 55665462 | 55665462 | C/T | 4 × 10−5 | c.485G>A | p.(R162Q) | Likely pathogenic | PS4, PP5, PP3 |
| rs397516354 | |||||||||||||||
| P6 | 29 | M | Exercise | None | HCM | MYBPC3 | 11 | 47373030 | 47373030 | A/AC | None | c.51dupG | p.(S18Tfs*31) | Likely pathogenic | PVS1, PM2 |
| P7 | 19 | F | Sleep | Palpitations | HCM | MYBPC3 | 11 | 47359112 | 47359112 | T/C | None | c.2432A>G | p.(K811R) | Likely pathogenic | PM1, PM2, PP3, PP5 |
| rs375675796 | |||||||||||||||
| P8 | 19 | M | NA | None | HCM | MYBPC3 | 11 | 47372895 | 47372905 | CGTGTGCCCTCT/C | None/rs397515925 | c.177_187delAGAGGGCACAC | p.(E60Afs*49) | Likely pathogenic | PVS1 |
| P9 | 46 | F | Sleep | None | HCM | MYBPC3 | 11 | 47372960 | 47372960 | C/CG | None | c.121dupC | p.(R41Pfs*8) | Likely pathogenic | PVS1, PM2 |
| P10 | 40 | M | NA | NA | IF | TTN | 2 | 179440001 | 179440001 | T/A | None | c.70858A>T | p.(R23620*) | Likely pathogenic | PVS1, PM2 |
ACM arrhythmogenic cardiomyopathy, Alt alternate allele, cDNA coding DNA, Chr chromosome, DCM dilated cardiomyopathy, F female, HCM hypertrophic cardiomyopathy, IF idiopathic fibrosis, LP likely pathogenic, M male, MAF minor allele frequency, NA not available, P pathogenic, Ref reference allele
aGenomic position refers to GRCh37. The following transcripts were used: DSP: NM_004415.4; MYBPC3:NM_000256.3; PKP2:NM_001005242.2; TNNI3:NM_000363.4; TMEM43:NM_024334.2; TTN:NM_001267550.2
bMAF is based on total number of individuals in the Genome Aggregation Database (gnomAD)
cSee ACMG guidelines [12] for further information on classification criteria