Table 1.
Rare variants observed in the WPW cohort
| ID | Genes | Variants | Mutation _type |
Parent al studies |
AR IC |
Tho u |
gnomA D |
ExA C |
esp650 0 |
CAD D_ph red |
pLI | Inhe rita nce |
Ethn icity |
Phenotype |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| De novo variants in AF genes | ||||||||||||||
| WPW046 | ANK2 | NM_020977.3:c.5437A>G:p.(Lys1813Glu) | Missense | DN | 0 | 0 | NA | 0 | 0 | 32 | 1 | AD | C | WPW, SVT |
| WPW035 | NEBL | NM_006393.2:c.2473C>T:p.(His825Tyr) | Missense | DN | 0 | 0 | NA | 0 | 0 | 24.3 | 0 | n/a | C | WPW, SVT |
| WPW098 | PITX2 | NM_000325.5:c.194C>T:p.(Pro65Leu) | Missense | DN | 0 | 0 | 5.09E-06 | 0 | 0 | 26.5 | 0.98 | AD | C | WPW |
| WPW192 | PRDM16 | NM_022114.3:c.2666C>T:p.(Pro889Leu) | Missense | DN | 1 | 0 | 2.00E-04 | 2.00E-04 | 5.00E-04 | 32 | 1 | n/a | C | WPW, SVT |
| De novo variants in novel genes | ||||||||||||||
| WPW425 | FNIP1 | NM_133372.2:c.2753_2756del:p.(Lys918Argfs*9) | frameshift_deletion | DN | 0 | 0 | NA | 0 | 0 | NA | 1 | n/a | C | WPW, speech delay |
| WPW006 | RHBDF1 | NM_022450.3:c.1384G>A:p.(Gly462Arg) | Missense | DN | 0 | 0 | 4.28E-06 | 0 | 0 | 29.4 | 0 | n/a | C | WPW |
| WPW247 | RHBDF1 | NM_022450.3:c.47A>C:p.(Lys16Thr) | Missense | DN | 0 | 0 | NA | 0 | 0 | 24.5 | 0 | n/a | C | WPW, ADHD |
| WPW282 | WWP1 | NM_007013.3:c.1879A>T:p.(Met627Leu) | Missense | DN | 0 | 0 | NA | 0 | 0 | 27.7 | 1 | AA | WPW, SVT | |
| Rare variants in known WPW genes | ||||||||||||||
| WPW423 | PRKAG2 | NM_016203.3:c.359G>A:p.(Arg120His) | Missense | N/A | 0 | 0 | 0.0001 | 0.00008261 | 0 | 34 | 1 | AD/AR | H | WPW and Ebstein anomaly |
| WPW238 | MYH6 | NM_002471.3:c.4430G>T:p.(Arg1477Leu) | Missense | N/A | 0 | 0 | 4.07E-06 | 0 | 0 | 35 | 0 | AD | AA | WPW |
| WPW385 | MYH7 | NM_000257.3:c.2389G>A:p.(Ala797Thr) | Missense | Inherited | 0 | 0 | 2.03E-05 | 3.30E-05 | 7.70E-05 | 20.5 | 0 | AD | C | WPW, SVT, new diagnosis of LVH |
| WPW381 | MYH7 | NM_000257.3:c.728G>A:p.(Arg243His) | Missense | Inherited | 0 | 0 | 8.12E-06 | 8.24E-06 | 0 | 34 | 0 | AD | C | WPW and LV non compaction cardiomyopathy |
| High CADD score (≥30) variants observed in WPW cohort in cardiac arrhythmia and cardiomyopathy genes | ||||||||||||||
| WPW052 | ACTN2 | NM_001103.3:c.2075T>A:p.(Ile692Asn) | Missense | Inherited | 0 | 0 | NA | 0 | 0 | 33 | 1 | AD | C | WPW, SVT |
| WPW108 | AKAP9 | NM_147185.2:c.11273G>A:p.(Arg3758Gln) | Missense | N/A | 0 | 5.00E-04 | 1.00E-04 | 1.00E-04 | 7.70E-05 | 34 | 0 | AD | C | WPW |
| WPW075 | ANK2 | NM_020977.3:c.742G>A:p.(Val248Met) | Missense | N/A | 0 | 0 | 1.22E-05 | 1.65E-05 | 0 | 33 | 1 | AD | C | WPW, SVT, cardiomegaly |
| WPW006 | KCNQ1 | NM_181798.1:c.1240G>A:p.(Val414Ile) | Missense | Inherited | 0 | 0 | 1.69E-05 | 3.87E-05 | 0 | 32 | 0 | AD/AR | C | WPW |
| WPW079 | KCNQ1 | NM_181798.1:c.343G>A:p.(Asp115Asn) | Missense | Inherited | 0 | 0 | 4.09E-06 | 8.67E-06 | 0 | 32 | 0 | AD/AR | AA | WPW, SVT, and LQTS; has a sister with LQTS |
| WPW238 | KCNQ1 | NM_181798.1:c.808C>T:p.(Arg270Trp) | Missense | N/A | 0 | 0 | 2.00E-04 | 2.00E-04 | 4.00E-04 | 33 | 0 | AD/AR | AA | WPW |
| WPW126 | LAMA4 | NM_001105207.2:c.2377C>T:p.(Arg793Cys) | Missense | Inherited | 7 | 0 | 7.32E-05 | 8.27E-05 | 5.00E-04 | 33 | 0 | n/a | AA | WPW, LV non compaction cardiomyopathy, and VSD |
| WPW416 | MYBPC3 | NM_000256.3:c.1219G>C:p.(Gly407Arg) | Missense | N/A | 0 | 0 | 9.68E-06 | 0 | 0 | 33 | 0 | AD | H | WPW, SVT |
| WPW077 | PRDM16 | NM_022114.3:c.2855C>T:p.(Thr952Met) | Missense | Inherited | 0 | 0 | 2.49E-05 | 9.05E-06 | 0 | 33 | 1 | H | WPW, SVT, ASD, VSD, hypothyroidism | |
| WPW101 | TTN | NM_133432.3:c.40459C>T:p.(Arg13487*) | stopgain | Inherited | 0 | 0 | 4.08E-06 | 0 | 0 | 62 | 0 | AD/AR | C | WPW, SVT |
| WPW416 | TTN | NM_133432.3:c.65863C>T:p.(Arg21955*) | stopgain | N/A | 0 | 0 | NA | 0 | 0 | 67 | 0 | AD/AR | H | WPW, SVT |
| Other rare variants in WPW cohort in cardiac arrhythmia and cardiomyopathy genes | ||||||||||||||
| WPW075 | ACTC1 | NM_005159.4:c.944T>A:p.(Met315Lys) | Missense | N/A | 0 | 0 | NA | 0 | 0 | 29 | 0.74 | AD | C | WPW, SVT, cardiomegaly |
| WPW306 | ACTC1 | NM_005159.4:c.524_525insC:p.(Ala176Cysfs*14) | frameshift_insertion | Inherited | 0 | 0 | NA | 0 | 0 | NA | 0.74 | AD | C | WPW, SVT, and subaortic stenosis |
| WPW279 | ANK2 | NM_020977.3:c.1427A>G:p.(Gln476Arg) | Missense | Inherited | 0 | 0 | NA | 0 | 0 | 28.2 | 1 | AD | C | WPW, SVT |
| WPW079 | CACNA1C | NM_001129842.1:c.1485C>A:p.(His495Gln) | nonsynonymous_SNV/exonic_splicing | Inherited | 2 | 0 | 2.84E-05 | 4.14E-05 | 8.30E-05 | 14.54 | 1 | AD | AA | WPW, SVT, and LQTS; has a sister with LQTS |
| WPW199 | JUP | NM_021991.3:c.773A>G:p.(Glu258Gly) | Missense | N/A | 0 | 0 | NA | 0 | 0 | 29.1 | 0 | AD/AR | AA | WPW |
| WPW209 | LAMA4 | NM_001105207.2:c.1399G>T:p.(Val467Phe) | Missense | Inherited | 0 | 0 | 4.06E-06 | 0 | 0 | 29.5 | 0 | n/a | H | WPW, SVT, and Ebstein anomaly |
| WPW312 | SCN5A | NM_001099405.1:c.1705C>G:p.(Arg569Gly) | Missense | N/A | 0 | 0 | NA | 0 | 0 | 25 | 0.91 | AD/AR | C | WPW |
| WPW159 | SCN5A | NM_001099405.1:c.1567C>T:p.(Arg523Cys) | Missense | Inherited | 0 | 0 | 8.47E-06 | 0 | 0 | 24.5 | 0.91 | AD/AR | H/C | WPW |
DN: de novo
SVT: supraventricular tachycardia
Blue font indicates variants designated to be pathogenic/likely pathogenic in ClinVar