KCNH2 (hERG) variants and mutations
KCNH2 (also known as hERG) is a human protein-coding gene encoding a voltage-gated inwardly rectifying potassium channel protein. Its unusually rapid inactivation and slow deactivation shape the rapid delayed-rectifier current IKr, a major determinant of ventricular repolarization. Loss-of-function variants can prolong repolarization and cause long-QT syndrome, whereas gain-of-function variants can cause short-QT syndrome. This analysis covers 2,412 KCNH2 variants and mutations. Of these, 90% have computational variant effect predictions. Disease context includes Romano-Ward syndrome, Familial short QT syndrome, and atrial fibrillation. Example KCNH2 variants include M1?, M1I, and P2L.
Variant analysis overview
- Gene: KCNH2
- Protein: hERG
- UniProt accession: Q12809
- Organism: Homo sapiens
- Variants analyzed: 2412
- Variant scope: all variants
- Completed: 2026-08-14
Variant and mutation evidence
- Variant composition: 2,176 unspecified-consequence records; 1 stop retained variant; 84 synonymous variants; 118 missense variants; 6 stop-gained variants; 14 frameshift variants; 2 splice-region variants; 1 protein altering variant; 1 in-frame deletions; 9 substitution
- Prediction scores: 2,167 variants have prediction scores (90% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Romano-Ward syndrome, Familial short QT syndrome, atrial fibrillation, cardiac arrhythmia, Prolonged QT interval, familial long QT syndrome, ventricular fibrillation, ventricular tachycardia, atrial flutter, multiple sclerosis, Ventricular arrhythmia, Abnormality of the cardiovascular system.
Protein structure and variant hotspots
- Protein features: 6 transmembrane segments; 2 domains; 11 post-translational modification sites.
- Structural context: 379 variants have structural context.
- PTM context: 21 variants overlap post-translational modification sites.
- Experimental data: 1,100 protein positions have experimental scores. Source: trafficking assays.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable KCNH2 variants
Examples include M1?, M1I, P2L, V3L, R4Q, G6D, V8G, A9T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, rs199473036, ClinGen CA006152, NCI-TCGA Cosmic COSV5117, ClinVar RCV000058074, MetaLR 0.98, MetaSVM 1.06, Variant assessed as somatic; high impact.
- M1I (p.Met1Ile), rs2117072816, ClinGen CA369866793, ClinVar RCV002031801, MetaLR 0.98, MetaSVM 1.06, Uncertain significance, Long QT syndrome
- P2L (p.Pro2Leu), rs2486167541, ClinGen CA369866785, ClinVar RCV002931984, REVEL 0.83, CADD 24.90, Uncertain significance, Long QT syndrome
- V3L (p.Val3Leu), rs2486167529, ClinGen CA369866783, ClinVar RCV004015333, NCI-TCGA TCGA novel, REVEL 0.57, CADD 23.50, Uncertain significance, Long QT syndrome
- R4Q (p.Arg4Gln), NCI-TCGA Cosmic COSV5121, REVEL 0.67, CADD 25.80, Variant assessed as somatic; moderate impact.
- G6D (p.Gly6Asp), rs2486167474, ClinGen CA369866762, ClinVar RCV004016226, REVEL 0.86, CADD 26.30, Uncertain significance, Long QT syndrome
- V8G (p.Val8Gly), rs2486167432, ClinGen CA369866747, ClinVar RCV004012421, Uncertain significance, Long QT syndrome
- A9T (p.Ala9Thr), gnomAD rs1348684482, REVEL 0.58, CADD 25.50
- A9V (p.Ala9Val), rs775317201, ClinGen CA007185, ClinVar RCV000181953, ClinVar RCV000469823, REVEL 0.72, CADD 26.50, Uncertain significance, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- P10L (p.Pro10Leu), rs1383782501, ClinGen CA369866736, ClinVar RCV001217948, ClinVar RCV006545987, REVEL 0.62, CADD 22.80, Uncertain significance, Cardiac arrhythmia; Long QT syndrome
- P10Q (p.Pro10Gln), rs1383782501, ClinGen CA369866738, NCI-TCGA Cosmic COSV1000, ClinVar RCV002051215, REVEL 0.83, CADD 25.90, Uncertain significance, Long QT syndrome
- Q11* (p.Gln11Ter), rs794728416, ClinGen CA008102, ClinVar RCV000181951, ClinVar RCV002516851, Pathogenic
- Q11L (p.Gln11Leu), TOPMed rs1156510876, gnomAD rs1156510876, REVEL 0.76, CADD 24.60, Uncertain significance, Long QT syndrome; Cardiac arrhythmia
- Q11R (p.Gln11Arg), rs1156510876, ClinGen CA369866733, ClinVar RCV001373121, TOPMed rs1156510876, REVEL 0.74, CADD 23.90, Uncertain significance, Long QT syndrome
- N12D (p.Asn12Asp), rs1412463792, ClinGen CA369866727, ClinVar RCV002050417, gnomAD rs1412463792, REVEL 0.68, AlphaMissense 0.98, Uncertain significance, Long QT syndrome
- N12H (p.Asn12His), rs1412463792, ClinGen CA369866728, ClinVar RCV001898215, gnomAD rs1412463792, REVEL 0.70, AlphaMissense 0.98, Uncertain significance, Long QT syndrome
- N12I (p.Asn12Ile), rs2486167328, ClinGen CA369866723, ClinVar RCV004012478, Uncertain significance, Long QT syndrome
- N12Y (p.Asn12Tyr), rs1412463792, ClinGen CA369866726, ClinVar RCV001918570, gnomAD rs1412463792, AlphaMissense 0.98, MetaLR 0.97, Uncertain significance, Long QT syndrome
- T13I (p.Thr13Ile), rs758978727, ClinGen CA369866717, ClinVar RCV003648803, REVEL 0.75, CADD 24.80, Uncertain significance, Long QT syndrome
- T13N (p.Thr13Asn), rs758978727, ClinGen CA039255, ClinVar RCV001349592, ClinVar RCV001843182, REVEL 0.90, CADD 25.60, Conflicting interpretations, Short QT syndrome type 1; Long QT syndrome 2; Long QT syndrome
- F14Y (p.Phe14Tyr), rs2486167283, ClinGen CA369866709, ClinVar RCV003049327, Uncertain significance, Long QT syndrome
- L15P (p.Leu15Pro), NCI-TCGA Cosmic COSV1000, Variant assessed as somatic; moderate impact.
- L15Q (p.Leu15Gln), rs794728418, ClinGen CA008465, ClinVar RCV000181954, Ensembl rs794728418, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, not provided
- L15R (p.Leu15Arg), rs794728418, ClinGen CA369866696, ClinVar RCV001574396, ClinVar RCV003647841, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, not provided; Long QT syndrome
- L15V (p.Leu15Val), rs1452324629, ClinGen CA369866700, ClinVar RCV002756695, gnomAD rs1452324629, REVEL 0.73, CADD 24.50, Uncertain significance, Long QT syndrome
- D16A (p.Asp16Ala), rs199472825, ClinGen CA008513, ClinVar RCV000058236, ClinVar RCV006547584, REVEL 0.78, AlphaMissense 0.98, Uncertain significance, Cardiac arrhythmia
- D16E (p.Asp16Glu), rs746628164, ClinGen CA039817, ClinVar RCV002574293, ExAC rs746628164, REVEL 0.47, CADD 22.20, Uncertain significance, Long QT syndrome
- D16G (p.Asp16Gly), rs199472825, ClinGen CA369866692, ClinVar RCV003311165, ClinVar RCV003647973, AlphaMissense 0.98, MetaLR 0.94, Uncertain significance, Cardiovascular phenotype; Long QT syndrome
- D16H (p.Asp16His), rs770772057, ClinGen CA369866694, ClinVar RCV003234472, ClinVar RCV004009686, REVEL 0.79, CADD 24.30, Uncertain significance, Long QT syndrome; not provided
- D16N (p.Asp16Asn), ExAC rs770772057, gnomAD rs770772057, MetaLR 0.84, MetaSVM 0.78, Uncertain significance, Long QT syndrome
- T17I (p.Thr17Ile), rs2117072638, ClinGen CA369866679, ClinVar RCV001974163, Ensembl rs2117072638, AlphaMissense 0.78, MetaLR 0.96, Uncertain significance, Long QT syndrome
- T17P (p.Thr17Pro), rs2486167222, ClinGen CA369866687, ClinVar RCV004007961, ClinVar RCV005587559, Uncertain significance, Long QT syndrome; Cardiovascular phenotype
- I18L (p.Ile18Leu), rs1012070155, ClinGen CA369866677, ClinVar RCV004015577, AlphaMissense 0.59, MetaLR 0.94, Uncertain significance, Long QT syndrome
- I18M (p.Ile18Met), ExAC rs772587513, gnomAD rs772587513, REVEL 0.83, CADD 25.70, Uncertain significance, Cardiac arrhythmia
- I18V (p.Ile18Val), Ensembl rs1012070155, REVEL 0.52, AlphaMissense 0.59
- I19F (p.Ile19Phe), rs1554431444, ClinGen CA369866667, ClinVar RCV000631726, Ensembl rs1554431444, AlphaMissense 0.99, MetaLR 0.96, Uncertain significance, Long QT syndrome
- I19S (p.Ile19Ser), rs1802016246, ClinGen CA369866664, ClinVar RCV001221141, Ensembl rs1802016246, AlphaMissense 1.00, MetaLR 0.97, Conflicting interpretations, Cardiovascular phenotype; Long QT syndrome
- I19T (p.Ile19Thr), rs1802016246, ClinVar RCV004595409, AlphaMissense 1.00, MetaLR 0.97, Uncertain significance, Long QT syndrome 2
- R20G (p.Arg20Gly), rs199473486, ClinGen CA008617, ClinVar RCV000058242, ClinVar RCV001571031, AlphaMissense 0.97, MetaLR 0.96, Uncertain significance, Long QT syndrome; not provided
- R20L (p.Arg20Leu), NCI-TCGA TCGA novel, REVEL 0.83, CADD 24.50, Uncertain significance, in LQT2
- R20P (p.Arg20Pro), rs2486167154, ClinGen CA369866657, ClinVar RCV003036815, Uncertain significance, Long QT syndrome
- F22C (p.Phe22Cys), rs199472826, ClinGen CA369866638, ClinVar RCV004010181, REVEL 0.78, AlphaMissense 1.00, Uncertain significance, Long QT syndrome
- F22S (p.Phe22Ser), rs199472826, ClinGen CA008663, ClinVar RCV000058246, Ensembl rs199472826, AlphaMissense 1.00, MetaLR 0.96, not provided, Congenital long QT syndrome
- F22V (p.Phe22Val), rs2117072572, ClinGen CA369866641, ClinVar RCV001973145, ClinVar RCV004044696, REVEL 0.83, CADD 32.00, Uncertain significance, Cardiovascular phenotype; Long QT syndrome
- E23* (p.Glu23Ter), rs1554431441, ClinGen CA658797054, ClinVar RCV000631592, CADD 39.00, Pathogenic
- G24C (p.Gly24Cys), TOPMed rs1802015908
- Q25H (p.Gln25His), rs2486167077, ClinGen CA369866601, ClinVar RCV003648719, ClinVar RCV005255768, REVEL 0.66, CADD 23.80, Uncertain significance, Long QT syndrome; not provided; Cardiac arrhythmia
- Q25L (p.Gln25Leu), rs1325360828, ClinGen CA369866605, ClinVar RCV004012154, REVEL 0.60, CADD 26.20, Uncertain significance, Long QT syndrome
- Q25P (p.Gln25Pro), gnomAD rs1325360828, REVEL 0.77, CADD 24.80
- S26G (p.Ser26Gly), rs1802015752, ClinGen CA369866596, ClinVar RCV001841151, ClinVar RCV002560988, REVEL 0.40, CADD 22.50, Uncertain significance, Cardiac arrhythmia; Long QT syndrome
- S26I (p.Ser26Ile), rs199472827, ClinGen CA008810, ClinVar RCV000058257, UniProt VAR 068249, REVEL 0.71, CADD 28.60, not provided, Congenital long QT syndrome
- S26T (p.Ser26Thr), rs878853772, Uncertain significance
- R27H (p.Arg27His), rs199472828, ClinGen CA008830, ClinVar RCV000181921, ClinVar RCV001213481, REVEL 0.76, AlphaMissense 0.96, Conflicting interpretations, not provided; Long QT syndrome
- R27P (p.Arg27Pro), rs199472828, ClinGen CA008838, ClinVar RCV000058259, ExAC rs199472828, AlphaMissense 0.96, MetaLR 0.96, not provided, Congenital long QT syndrome
- K28* (p.Lys28Ter), rs794728475, ClinGen CA305341, ClinVar RCV000182015, ClinVar RCV001064849, CADD 33.00, Pathogenic
- K28E (p.Lys28Glu), rs199472829, ClinGen CA008871, ClinVar RCV000058261, Ensembl rs199472829, AlphaMissense 0.88, MetaLR 0.96, Pathogenic, Congenital long QT syndrome
- K28N (p.Lys28Asn), rs1584883517, ClinGen CA915945560, ClinVar RCV000799458, REVEL 0.62, CADD 23.10, Pathogenic
- K28R (p.Lys28Arg), rs2486157311, ClinGen CA369866034, ClinVar RCV004012502, Uncertain significance, Long QT syndrome
- F29L (p.Phe29Leu), rs199472830, ClinGen CA369866018, ClinVar RCV002373704, UniProt VAR 008907, REVEL 0.84, CADD 25.00, Likely pathogenic, Long QT syndrome
- F29S (p.Phe29Ser), rs199472831, ClinGen CA008920, ClinVar RCV000058265, Ensembl rs199472831, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, Long QT syndrome
- I30T (p.Ile30Thr), rs199472832, ClinGen CA008968, ClinVar RCV000058270, ClinVar RCV000690304, AlphaMissense 0.98, MetaLR 0.95, Uncertain significance, Long QT syndrome
- I31M (p.Ile31Met), rs745885744, ClinGen CA369865996, ClinVar RCV001040868, ExAC rs745885744, AlphaMissense 0.97, MetaLR 0.98, Uncertain significance, Long QT syndrome
- I31S (p.Ile31Ser), rs199472833, ClinGen CA009002, ClinVar RCV000058275, UniProt VAR 068250, AlphaMissense 1.00, MetaLR 0.99, not provided, Congenital long QT syndrome
- I31T (p.Ile31Thr), rs199472833, ClinGen CA008995, ClinVar RCV000058274, ClinVar RCV000181922, AlphaMissense 1.00, MetaLR 0.99, Likely pathogenic, not provided
- I31N (p.Ile31Asn), rs199472833, ClinGen CA369865998, ClinVar RCV000624163, Ensembl rs199472833, AlphaMissense 1.00, MetaLR 0.99, Likely pathogenic, Long QT syndrome 2
- A32T (p.Ala32Thr), rs199472834, ClinGen CA009024, ClinVar RCV000058278, ClinVar RCV001841762, REVEL 0.83, CADD 32.00, Uncertain significance, Cardiac arrhythmia; Long QT syndrome
- A32V (p.Ala32Val), rs1801941580, ClinGen CA369865988, ClinVar RCV001089534, Ensembl rs1801941580, AlphaMissense 0.99, MetaLR 0.98, Pathogenic, Long QT syndrome 2
- N33K (p.Asn33Lys), rs2486157141, ClinGen CA369865976, ClinVar RCV003534008, REVEL 0.76, CADD 27.30, Uncertain significance, Long QT syndrome
- N33S (p.Asn33Ser), rs199473487, ClinGen CA369865980, ClinVar RCV002224220, ClinVar RCV003089165, AlphaMissense 0.80, MetaLR 0.96, Uncertain significance, Long QT syndrome; not provided
- N33T (p.Asn33Thr), rs199473487, ClinGen CA009070, ClinVar RCV000058282, ClinVar RCV000780363, AlphaMissense 0.80, MetaLR 0.96, Conflicting interpretations, Cardiac arrhythmia; Cardiovascular phenotype; not provided
- A34D (p.Ala34Asp), NCI-TCGA TCGA novel, CADD 20.20, Variant assessed as somatic; moderate impact.
- A34T (p.Ala34Thr), gnomAD rs1481808066, CADD 20.70, Uncertain significance, not provided
- A34V (p.Ala34Val), TOPMed rs1801941190, CADD 20.60, Likely benign, Long QT syndrome
- R35P (p.Arg35Pro), rs1801941054, ClinGen CA369865955, ClinVar RCV002401158, REVEL 0.84, CADD 26.50, Uncertain significance, Cardiovascular phenotype
- R35Q (p.Arg35Gln), Ensembl rs1801941054, REVEL 0.47, CADD 20.60
- R35W (p.Arg35Trp), rs2117063783, ClinGen CA369865959, ClinVar RCV001901315, Ensembl rs2117063783, AlphaMissense 0.76, MetaLR 0.97, Uncertain significance, Long QT syndrome
- V36G (p.Val36Gly), TOPMed rs1427593456, gnomAD rs1427593456, REVEL 0.76, CADD 29.90
- N38K (p.Asn38Lys), rs2117063715, ClinGen CA369865916, ClinVar RCV001991634, Ensembl rs2117063715, AlphaMissense 0.90, MetaLR 0.96, Uncertain significance, Long QT syndrome
- N38S (p.Asn38Ser), TOPMed rs1314433712, MetaLR 0.95, MetaSVM 1.07
- C39G (p.Cys39Gly), ExAC rs757491162, TOPMed rs757491162, gnomAD rs757491162, Uncertain significance
- C39R (p.Cys39Arg), rs757491162, ClinGen CA027276, ClinVar RCV000559174, ClinVar RCV002358441, REVEL 0.93, CADD 32.00, Uncertain significance, KCNH2-related disorder; Cardiac arrhythmia; Cardiovascular phenotype
- C39Y (p.Cys39Tyr), rs2486157018, ClinGen CA369865909, ClinVar RCV003648822, Uncertain significance, Long QT syndrome
- A40V (p.Ala40Val), rs794728407, ClinGen CA004270, ClinVar RCV000181924, Ensembl rs794728407, AlphaMissense 0.84, MetaLR 0.96, Likely pathogenic, not provided
- V41A (p.Val41Ala), rs731506, ClinGen CA004307, ClinVar RCV000057876, Ensembl rs731506, AlphaMissense 0.96, MetaLR 0.97, not provided, Congenital long QT syndrome
- V41F (p.Val41Phe), rs199472835, ClinGen CA004285, ClinVar RCV000057874, UniProt VAR 074769, AlphaMissense 0.84, MetaLR 0.91, not provided, Congenital long QT syndrome
- V41G (p.Val41Gly), Ensembl rs731506, Uncertain significance, in LQT2
- V41L (p.Val41Leu), rs199472835, ClinGen CA16042697, ClinVar RCV000412825, Ensembl rs199472835, AlphaMissense 0.84, MetaLR 0.91, Likely pathogenic, not provided
- I42F (p.Ile42Phe), rs1801940339, ClinVar RCV004556941, ClinVar RCV005100831, AlphaMissense 0.88, MetaLR 0.94, Conflicting interpretations, Long QT syndrome 2; Long QT syndrome
- I42N (p.Ile42Asn), rs199473488, ClinGen CA004330, ClinVar RCV000057879, Ensembl rs199473488, AlphaMissense 1.00, MetaLR 0.98, not provided, Congenital long QT syndrome
- I42T (p.Ile42Thr), rs199473488, ClinGen CA004336, ClinVar RCV000181925, ClinVar RCV003647756, AlphaMissense 1.00, MetaLR 0.98, Conflicting interpretations, not provided; Long QT syndrome
- I42V (p.Ile42Val), TOPMed rs1801940339, MetaLR 0.98, MetaSVM 1.08
- Y43C (p.Tyr43Cys), rs199472836, ClinGen CA004427, ClinVar RCV000057889, ClinVar RCV000181926, AlphaMissense 0.97, MetaLR 0.98, Pathogenic, not provided; Long QT syndrome; Long QT syndrome 2
- Y43D (p.Tyr43Asp), rs199472837, ClinGen CA004378, ClinVar RCV000057884, ClinVar RCV002247455, AlphaMissense 1.00, MetaLR 0.98, Pathogenic, Short QT syndrome type 1
- C44F (p.Cys44Phe), rs199473489, ClinGen CA004463, ClinVar RCV000057893, Ensembl rs199473489, AlphaMissense 1.00, MetaLR 0.99, not provided, Congenital long QT syndrome
- C44W (p.Cys44Trp), rs199472838, ClinGen CA004471, ClinVar RCV000057894, TOPMed rs199472838, AlphaMissense 1.00, MetaLR 0.99, not provided, Congenital long QT syndrome
- C44Y (p.Cys44Tyr), rs199473489, ClinGen CA369865856, ClinVar RCV001581933, ClinVar RCV003533011, AlphaMissense 1.00, MetaLR 0.99, Conflicting interpretations, not provided; Long QT syndrome
- N45D (p.Asn45Asp), Ensembl rs199472839, Uncertain significance, in LQT2
- N45K (p.Asn45Lys), rs1422251865, ClinGen CA369865838, ClinVar RCV003037273, ClinGen CA369865840, AlphaMissense 1.00, MetaLR 1.00, Uncertain significance, Long QT syndrome
- N45T (p.Asn45Thr), rs1801939758, ClinGen CA369865844, ClinVar RCV001220675, Ensembl rs1801939758, AlphaMissense 0.88, MetaLR 1.00, Uncertain significance, Long QT syndrome
- N45Y (p.Asn45Tyr), rs199472839, ClinGen CA004504, ClinVar RCV000057896, UniProt VAR 074771, AlphaMissense 0.96, MetaLR 1.00, not provided, Congenital long QT syndrome
- D46E (p.Asp46Glu), rs752503743, ClinGen CA027854, ClinVar RCV001843092, ClinVar RCV001876025, REVEL 0.61, CADD 23.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; Long QT syndrome
- D46G (p.Asp46Gly), rs2117063507, ClinGen CA369865832, ClinVar RCV001758260, ClinVar RCV002032795, AlphaMissense 0.93, MetaLR 0.98, Uncertain significance, not provided; Long QT syndrome
- D46N (p.Asp46Asn), rs794728408, ClinGen CA004535, ClinVar RCV000181928, ClinVar RCV003532023, REVEL 0.82, CADD 31.00, Uncertain significance, Cardiac arrhythmia; not provided; Long QT syndrome
- G47C (p.Gly47Cys), rs794728409, ClinGen CA004565, ClinVar RCV000181929, ClinVar RCV001248792, AlphaMissense 0.76, MetaLR 0.99, Pathogenic/Likely pathogenic, Long QT syndrome 2; not provided
- G47D (p.Gly47Asp), gnomAD rs199473490, REVEL 0.95, AlphaMissense 0.79, Pathogenic, in LQT2
- G47R (p.Gly47Arg), rs794728409, ClinGen CA369865823, ClinVar RCV002903396, ClinVar RCV004617105, AlphaMissense 0.76, MetaLR 0.99, Uncertain significance, Long QT syndrome; Cardiovascular phenotype
- G47V (p.Gly47Val), rs199473490, ClinGen CA004581, ClinVar RCV000057903, ClinVar RCV002247456, AlphaMissense 0.79, MetaLR 0.98, Pathogenic, Short QT syndrome type 1
- C49* (p.Cys49Ter), rs1584883377, ClinGen CA915945559, ClinVar RCV000821345, ClinVar RCV002390696, Pathogenic, in LQT2
- C49F (p.Cys49Phe), rs199472840, ClinGen CA369865805, ClinVar RCV001248797, Ensembl rs199472840, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, Long QT syndrome 2
- C49W (p.Cys49Trp), rs794728410, ClinGen CA004708, ClinVar RCV000181930, gnomAD rs794728410, AlphaMissense 1.00, MetaLR 0.97, Pathogenic, not provided
- C49Y (p.Cys49Tyr), rs199472840, ClinGen CA004664, ClinVar RCV000057912, UniProt VAR 074772, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, Long QT syndrome
- E50D (p.Glu50Asp), rs199472841, ClinGen CA004747, ClinVar RCV000057920, ClinVar RCV002514285, REVEL 0.62, CADD 17.50, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; Long QT syndrome
- E50Q (p.Glu50Gln), rs1801938958, ClinGen CA369865802, ClinVar RCV001204379, TOPMed rs1801938958, AlphaMissense 0.09, MetaLR 0.94, Uncertain significance, Long QT syndrome
- L51P (p.Leu51Pro), rs2486156624, ClinGen CA369865794, ClinVar RCV003534281, Uncertain significance, Long QT syndrome
- C52* (p.Cys52Ter), rs754921704, ClinGen CA004804, ClinVar RCV001236747, ExAC rs754921704, CADD 33.00, Pathogenic
- C52A (p.Cys52Ala), rs794728508, ClinGen CA004782, ClinVar RCV000796540, ClinVar RCV001842865, Pathogenic
- C52W (p.Cys52Trp), rs754921704, ClinGen CA028777, ClinVar RCV001248114, ExAC rs754921704, REVEL 0.55, CADD 20.90, Uncertain significance, Long QT syndrome
- G53C (p.Gly53Cys), rs199472842, ClinGen CA369865785, ClinVar RCV002010371, ClinVar RCV002398079, AlphaMissense 0.65, MetaLR 0.99, Conflicting interpretations, Long QT syndrome; Cardiovascular phenotype
- G53D (p.Gly53Asp), rs199473491, ClinGen CA004864, ClinVar RCV000057926, ClinVar RCV003326345, AlphaMissense 0.94, MetaLR 1.00, Uncertain significance, Cardiovascular phenotype; Cardiac arrhythmia; Long QT syndrome
- G53R (p.Gly53Arg), rs199472842, ClinGen CA004831, ClinVar RCV000057924, ClinVar RCV001267970, AlphaMissense 0.65, MetaLR 0.99, Uncertain significance, Cardiac arrhythmia; Cardiovascular phenotype; Congenital long QT syndrome
- G53S (p.Gly53Ser), rs199472842, ClinGen CA004823, ClinVar RCV000057923, Ensembl rs199472842, AlphaMissense 0.65, MetaLR 0.99, not provided, Congenital long QT syndrome
- Y54* (p.Tyr54Ter), rs1554430962, ClinGen CA369865774, ClinVar RCV000618350, Ensembl rs1554430962, Pathogenic, in LQT2
- Y54H (p.Tyr54His), rs199472843, ClinGen CA004937, ClinVar RCV000057932, ClinVar RCV001854195, AlphaMissense 0.90, MetaLR 0.99, Conflicting interpretations, Cardiovascular phenotype; Long QT syndrome; Long QT syndrome 2
- S55* (p.Ser55Ter), rs199472844, ClinGen CA16618417, ClinVar RCV000484322, ClinVar RCV001239959, AlphaMissense 0.59, MetaLR 0.98, Pathogenic, in LQT2
- S55L (p.Ser55Leu), rs199472844, ClinGen CA004951, ClinVar RCV000057933, ClinVar RCV000182049, REVEL 0.93, AlphaMissense 0.59, Conflicting interpretations, Cardiovascular phenotype; not provided; Long QT syndrome
- S55W (p.Ser55Trp), rs199472844, ClinGen CA369865767, ClinVar RCV003647723, AlphaMissense 0.59, MetaLR 0.98, Uncertain significance, Long QT syndrome
- R56G (p.Arg56Gly), TOPMed rs1801937245, Likely benign, in LQT2
- R56L (p.Arg56Leu), rs199472845, ClinGen CA005012, ClinVar RCV000181931, ClinVar RCV000461590, REVEL 0.81, AlphaMissense 1.00, Pathogenic/Likely pathogenic, not provided; Long QT syndrome
- R56P (p.Arg56Pro), rs199472845, ClinGen CA369865760, ClinVar RCV002406011, REVEL 0.87, AlphaMissense 1.00, Uncertain significance, Cardiovascular phenotype
- R56Q (p.Arg56Gln), rs199472845, ClinGen CA005006, ClinVar RCV000057938, ClinVar RCV000462413, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, Long QT syndrome
- A57P (p.Ala57Pro), rs199472846, ClinGen CA005160, ClinVar RCV000057951, ClinVar RCV001212247, AlphaMissense 0.33, MetaLR 0.96, Uncertain significance, Long QT syndrome
- A57S (p.Ala57Ser), rs199472846, ClinGen CA369865754, ClinVar RCV003531772, REVEL 0.47, AlphaMissense 0.33, Uncertain significance, Long QT syndrome
- A57T (p.Ala57Thr), rs199472846, ClinGen CA369865757, ClinVar RCV000810996, TOPMed rs199472846, REVEL 0.51, AlphaMissense 0.33, Uncertain significance, Long QT syndrome
- A57V (p.Ala57Val), rs794728493, ClinGen CA005221, ClinVar RCV000182050, ClinVar RCV001852297, AlphaMissense 0.38, MetaLR 0.97, Conflicting interpretations, not provided; Long QT syndrome
- E58* (p.Glu58Ter), rs199473413, ClinGen CA369865747, ClinVar RCV003531706, AlphaMissense 0.98, MetaLR 0.99, Pathogenic, in LQT2
- E58A (p.Glu58Ala), rs199472847, ClinGen CA005322, ClinVar RCV000057968, UniProt VAR 074776, AlphaMissense 0.83, MetaLR 0.98, not provided, Congenital long QT syndrome
- E58D (p.Glu58Asp), rs199473492, ClinGen CA005364, ClinVar RCV000057973, UniProt VAR 074777, AlphaMissense 0.42, MetaLR 0.96, not provided, Congenital long QT syndrome
- E58G (p.Glu58Gly), rs199472847, ClinGen CA005331, ClinVar RCV000057969, ClinVar RCV000181920, AlphaMissense 0.83, MetaLR 0.98, Likely pathogenic, not provided
- E58K (p.Glu58Lys), rs199473413, ClinGen CA005294, ClinVar RCV000057966, ClinVar RCV000472868, AlphaMissense 0.98, MetaLR 0.99, Pathogenic/Likely pathogenic, Cardiovascular phenotype; not provided; Long QT syndrome
- E58Q (p.Glu58Gln), rs199473413, ClinGen CA369865745, ClinVar RCV003819429, AlphaMissense 0.98, MetaLR 0.99, Uncertain significance, Long QT syndrome
- M60I (p.Met60Ile), rs2486156355, ClinGen CA369865716, ClinVar RCV002800772, Uncertain significance, Long QT syndrome
- Q61R (p.Gln61Arg), rs2486156328, ClinGen CA369865705, ClinVar RCV003531550, Uncertain significance, Cardiovascular phenotype; Long QT syndrome
- R62Q (p.Arg62Gln), rs199473664, ClinGen CA005697, ClinVar RCV000058016, ClinVar RCV001215033, REVEL 0.65, CADD 23.00, Uncertain significance, Long QT syndrome
- P63H (p.Pro63His), rs766379103, ClinGen CA005881, ClinVar RCV000181932, ClinVar RCV000631676, REVEL 0.81, AlphaMissense 0.88, Conflicting interpretations, Cardiovascular phenotype; not provided; Long QT syndrome
- P63L (p.Pro63Leu), rs766379103, ClinGen CA369865681, ClinVar RCV001902021, ExAC rs766379103, AlphaMissense 0.88, MetaLR 0.98, Uncertain significance, Long QT syndrome
- C64W (p.Cys64Trp), rs199473414, ClinGen CA006038, ClinVar RCV000058057, UniProt VAR 074779, AlphaMissense 1.00, MetaLR 0.98, not provided, Congenital long QT syndrome
- C64Y (p.Cys64Tyr), rs199473415, ClinGen CA006024, ClinVar RCV000058054, UniProt VAR 077953, AlphaMissense 0.99, MetaLR 0.99, not provided, Congenital long QT syndrome
- T65A (p.Thr65Ala), TOPMed rs121912511, Pathogenic, in LQT2
- T65P (p.Thr65Pro), rs121912511, ClinGen CA006061, ClinVar RCV000015515, ClinVar RCV000058063, AlphaMissense 0.37, MetaLR 0.98, Pathogenic, Long QT syndrome 2
- T65S (p.Thr65Ser), rs878853772, ClinGen CA10582468, ClinVar RCV000231224, ClinVar RCV004739629, REVEL 0.68, CADD 25.20, Uncertain significance, Long QT syndrome
- C66* (p.Cys66Ter), rs1801935667, ClinGen CA369865646, ClinVar RCV001070384, Ensembl rs1801935667, Pathogenic, in LQT2
- C66G (p.Cys66Gly), rs199473416, ClinGen CA006132, ClinVar RCV000058071, UniProt VAR 008911, AlphaMissense 1.00, MetaLR 0.99, not provided, Congenital long QT syndrome
- C66R (p.Cys66Arg), rs199473416, ClinGen CA369865654, ClinVar RCV000553516, Ensembl rs199473416, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, Long QT syndrome
- C66W (p.Cys66Trp), NCI-TCGA TCGA novel, Uncertain significance, Long QT syndrome
- C66Y (p.Cys66Tyr), rs1554430943, ClinGen CA369865648, ClinVar RCV000656723, ClinVar RCV002534252, AlphaMissense 1.00, MetaLR 0.99, Conflicting interpretations, Long QT syndrome; Long QT syndrome 2
- D67G (p.Asp67Gly), rs1801935588, ClinGen CA369865634, ClinVar RCV001352272, Ensembl rs1801935588, AlphaMissense 0.33, MetaLR 0.97, Uncertain significance, Long QT syndrome
- F68C (p.Phe68Cys), rs1801935420, ClinGen CA369865625, ClinVar RCV001209799, Ensembl rs1801935420, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, Long QT syndrome
- F68L (p.Phe68Leu), rs199473417, ClinGen CA006163, ClinVar RCV000058075, ClinVar RCV000181933, AlphaMissense 1.00, MetaLR 0.98, Conflicting interpretations, not provided; Cardiovascular phenotype
- L69P (p.Leu69Pro), rs199473665, ClinGen CA006187, ClinVar RCV000058078, ClinVar RCV002470746, AlphaMissense 1.00, MetaLR 0.99, Pathogenic, Long QT syndrome 2
- L69Q (p.Leu69Gln), rs199473665, ClinGen CA369865614, ClinVar RCV000624842, Ensembl rs199473665, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, Long QT syndrome
- H70N (p.His70Asn), rs199473418, ClinGen CA006222, ClinVar RCV000058082, UniProt VAR 074781, AlphaMissense 0.29, MetaLR 0.97, not provided, Congenital long QT syndrome
- H70Q (p.His70Gln), NCI-TCGA TCGA novel, Uncertain significance, in LQT2
- H70R (p.His70Arg), rs199473419, ClinGen CA006229, ClinVar RCV000058083, ClinVar RCV000181934, AlphaMissense 0.34, MetaLR 0.97, Pathogenic/Likely pathogenic, Cardiovascular phenotype; Long QT syndrome; not provided
- G71E (p.Gly71Glu), rs886039183, ClinGen CA10587642, ClinVar RCV000243747, ClinVar RCV002518733, AlphaMissense 1.00, MetaLR 0.99, Pathogenic/Likely pathogenic, Long QT syndrome; Cardiovascular phenotype
- G71R (p.Gly71Arg), rs199473420, ClinGen CA006261, ClinVar RCV000058086, ClinVar RCV000181935, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, not provided; Long QT syndrome
- G71W (p.Gly71Trp), rs199473420, ClinGen CA369865595, ClinVar RCV001058299, gnomAD rs199473420, AlphaMissense 1.00, MetaLR 0.99, Pathogenic, Long QT syndrome
- P72L (p.Pro72Leu), rs199473421, ClinGen CA006305, ClinVar RCV000058090, ClinVar RCV000181938, REVEL 0.90, AlphaMissense 0.54, Pathogenic/Likely pathogenic, Long QT syndrome; not provided; Cardiovascular phenotype
- P72Q (p.Pro72Gln), rs199473421, ClinGen CA006293, ClinVar RCV000058088, ClinVar RCV000463612, AlphaMissense 0.54, MetaLR 0.99, Pathogenic/Likely pathogenic, Cardiovascular phenotype; not provided; Long QT syndrome
- P72R (p.Pro72Arg), rs199473421, ClinGen CA006299, ClinVar RCV000058089, ClinVar RCV000464288, AlphaMissense 0.54, MetaLR 0.99, Likely pathogenic, Long QT syndrome
- P72S (p.Pro72Ser), rs794728411, ClinGen CA006286, ClinVar RCV000181936, ClinVar RCV002516850, AlphaMissense 0.42, MetaLR 0.98, Conflicting interpretations, not provided; Long QT syndrome
- R73C (p.Arg73Cys), ExAC rs767343755, gnomAD rs767343755, Uncertain significance, Cardiac arrhythmia
- R73H (p.Arg73His), TOPMed rs1456508280, gnomAD rs1456508280, REVEL 0.47, CADD 23.20
- T74A (p.Thr74Ala), rs199473666, ClinGen CA369865572, ClinVar RCV001344425, Ensembl rs199473666, AlphaMissense 0.93, MetaLR 0.99, Uncertain significance, Long QT syndrome
- T74C (p.Thr74Cys), rs2117062748, ClinGen CA2573141816, ClinVar RCV001956514, ClinVar RCV005585030, Pathogenic, in LQT2
- T74M (p.Thr74Met), rs199473422, ClinGen CA006365, ClinVar RCV000058097, ClinVar RCV000807020, AlphaMissense 0.98, MetaLR 0.98, Uncertain significance, Cardiovascular phenotype; Long QT syndrome
- T74P (p.Thr74Pro), rs199473666, ClinGen CA006352, ClinVar RCV000058095, UniProt VAR 074786, AlphaMissense 0.93, MetaLR 0.99, not provided, Congenital long QT syndrome
- T74R (p.Thr74Arg), rs1389503709, ClinGen CA835213821, ClinVar RCV001382272, ClinVar RCV001509332, Conflicting interpretations, Long QT syndrome; not provided
- Q75E (p.Gln75Glu), rs1801933977, ClinGen CA369865564, ClinVar RCV001323367, Ensembl rs1801933977, AlphaMissense 0.08, MetaLR 0.86, Uncertain significance, Long QT syndrome
- Q75H (p.Gln75His), TOPMed rs1801933890, REVEL 0.36, CADD 22.50, Likely benign
- R76H (p.Arg76His), gnomAD rs868054429, REVEL 0.60, CADD 26.20, Uncertain significance
Public KCNH2 analysis runs
- KCNH2 analysis run — KCNH2 (2,412 variants) — completed 2026-08-14
- KCNH2 analysis run — KCNH2 (2,412 variants) — completed 2026-07-17
- KCNH2 analysis run — KCNH2 (2,412 variants) — completed 2026-06-27
- KCNH2 analysis run — KCNH2 (2,397 variants) — completed 2026-05-29
- KCNH2 analysis run — KCNH2 (2,397 variants) — completed 2026-05-15