Table 4. Summary of non-ion channel rare variants associated with AF.
| Gene | Gene product | Nucleotide substitution | Amino-acid substitution | Documented family co-segregation | Electrophysiological consequence | Reference | Found in ESP EA minor/minor/ minor/major | Found in ESP AA minor/minor/ minor/major | Found in ESP all minor/minor/ minor/major |
|---|---|---|---|---|---|---|---|---|---|
| NUP155 | Nucleoporin | c.1172G>A | p.(Arg391His) | Yes | Loss-of-function | 77, 78 | 0/0 | 0/0 | 0/0 |
| GJA1 | Connexin43 | c.932delC | Frameshifta | No | Loss-of-function | 93 | 0/0 | 0/0 | 0/0 |
| GJA5 | Connexin40 | c.113G>A | p.(Gly38Asp)a | No | Loss-of-function | 94 | 0/0 | 0/0 | 0/0 |
| c.145C>T | p.(Gln49Ter) | Yes | Loss-of-function | 97 | 0/0 | 0/0 | 0/0 | ||
| c.223A>T | p.(Ile75Phe) | Yes | Loss-of-function | 98 | 0/0 | 0/0 | 0/0 | ||
| c.253G>A | p.(Val85Ile) | Yes | Not investigated | 96 | 0/0 | 0/0 | 0/0 | ||
| c.262C>T | p.(Pro88Ser)a | No | Loss-of-function | 94 | 0/0 | 0/0 | 0/0 | ||
| c.286G>T | p.(Ala96Ser) | No | Loss-of-function | 94 | 0/0 | 0/0 | 0/0 | ||
| c.487A>G | p.(Met163Val)a | No | Loss-of-function | 94 | 0/0 | 0/0 | 0/0 | ||
| c.661C>A | p.(Leu221Ile) | Yes | Not investigated | 96 | 0/0 | 0/0 | 0/0 | ||
| c.685C>A | p.(Leu229Met) | Yes | Not investigated | 96 | 0/0 | 0/0 | 0/0 | ||
| NPPA | ANP | c.190A>C | p.(Ser64Arg) | Yes | Gain-of-function | 52 | 0/24 | 0/2 | 0/26 |
| c.350C>T | p.(Ala117Val) | Yes | Not investigated | 117 | 0/0 | 0/0 | 0/0 | ||
| c.456_457delAA | Frameshift | Yes | Gain-of-function | 80 | 0/0 | 0/0 | 0/0 | ||
| GATA4 | Transcription factor | c.46G>T | p.(Gly16Cys) | Yes | Loss-of-function | 84 | 0/0 | 0/0 | 0/0 |
| c.82C>G | p.(His28Asp) | Yes | Loss-of-function | 84 | 0/0 | 0/0 | 0/0 | ||
| c.112T>G | p.(Tyr38Asp) | Yes | Loss-of-function | 85 | 0/0 | 0/0 | 0/0 | ||
| c.209G>C | p.(Ser70Thr) | Yes | Loss-of-function | 83 | 0/0 | 0/0 | 0/0 | ||
| c.307C>G | p.(Pro103Ala) | Yes | Loss-of-function | 85 | 0/0 | 0/0 | 0/0 | ||
| c.479G>C | p.(Ser160Thr) | Yes | Loss-of-function | 83 | 0/0 | 0/0 | 0/0 | ||
| c.1294C>T | p.(Met247Thr) | Yes | Not investigated | 82 | 0/0 | 0/0 | 0/0 | ||
| c.1786C>T | p.(Ala411Val) | No | Not investigated | 82 | 0/12 | 0/10 | 0/22 | ||
| GATA6 | Transcription factor | c.617A>C | p.(Gln206Pro) | Yes | Not investigated | 86 | 0/0 | 0/0 | 0/0 |
| c.704A>C | p.(Tyr235Ser) | Yes | Loss-of-function | 87 | 0/0 | 0/0 | 0/0 | ||
| c.795C>G | p.(Tyr265Ter) | Yes | Not investigated | 86 | 0/0 | 0/0 | 0/0 | ||
| c.1406G>T | p.(Gly469Val) | Yes | Loss-of-function | 88 | 0/0 | 0/0 | 0/0 | ||
| LMNA | Lamin A/C | c.78C>T | p.(Ile26Ile) | ? | ? | 91 | 0/2 | 0/0 | 0/2 |
| c.832G>A | p.(Ala278Thr) | Yes | Not investigated | 90 | 0/0 | 0/0 | 0/0 | ||
| c.1462A>C | p.(Thr488Pro) | No | Not investigated | 128 | 0/0 | 0/0 | 0/0 | ||
| c.1583C>T | p.(Thr528Met) | Yes | Not investigated | 91 | 0/0 | 0/0 | 0/0 | ||
| NKX2-5 | Transcription factor | c.434T>C | p.(Phe145Ser) | Yes | Not investigated | 117 | 0/0 | 0/0 | 0/0 |
| GREM2 | BMP antagonist | c.226C>G | p.(Gln76Glu) | No | Increase in inhibitory effect | 92 | 0/27 | 0/4 | 0/31 |
Abbreviations: AA, African American; EA, European American; ESP, NHLBI GO Exome Sequencing Project.
a
Somatic mutations.