RELN (Reelin) variants and mutations
RELN (also known as Reelin) is a human protein-coding gene encoding a reelin protein. It is secreted during brain development to guide neuronal migration and cortical layering and later modulates synaptic plasticity. Biallelic loss-of-function variants cause lissencephaly with cerebellar hypoplasia, while heterozygous variants can be associated with epilepsy. This analysis covers 4,727 RELN variants and mutations. Of these, 89% have computational variant effect predictions. Disease context includes Norman-Roberts syndrome, familial temporal lobe epilepsy 7, and Lissencephaly syndrome, Norman-Roberts type. Example RELN variants include M1V, E2A, and E2D.
Variant analysis overview
- Gene: RELN
- Protein: Reelin
- UniProt accession: P78509
- Organism: Homo sapiens
- Variants analyzed: 4727
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 4,577 unspecified-consequence records; 1 stop retained variant; 8 frameshift variants; 75 missense variants; 58 synonymous variants; 4 in-frame deletions; 1 stop-gained variants; 2 splice-region variants; 1 substitution
- Prediction scores: 4,207 variants have prediction scores (89% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Norman-Roberts syndrome, familial temporal lobe epilepsy 7, Lissencephaly syndrome, Norman-Roberts type, temporal lobe epilepsy, autosomal dominant epilepsy with auditory features, Rolandic epilepsy, self-limited epilepsy with centrotemporal spikes, Abnormality of the skeletal system, Lissencephaly, hereditary disease, otosclerosis, open-angle glaucoma.
Protein structure and variant hotspots
- Protein features: 9 domains; 7 binding sites; 19 post-translational modification sites.
- Structural context: 580 variants have structural context.
- PTM context: 33 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable RELN variants
Examples include M1V, E2A, E2D, E2G, E2Q, R3L, S4N, S4R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1V (p.Met1Val), rs1218893617, ClinGen CA368931665, ClinVar RCV001984604, MetaLR 0.04, MetaSVM -1.10, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- E2A (p.Glu2Ala), ExAC rs751188993, TOPMed rs751188993, gnomAD rs751188993, MetaLR 0.05, MetaSVM -1.06, Uncertain significance
- E2D (p.Glu2Asp), TOPMed rs1386205628, gnomAD rs1386205628, REVEL 0.06, MetaLR 0.04
- E2G (p.Glu2Gly), rs751188993, ClinGen CA4422746, ClinVar RCV002636962, ExAC rs751188993, REVEL 0.03, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- E2Q (p.Glu2Gln), ExAC rs754706510, gnomAD rs754706510, REVEL 0.03, MetaLR 0.05
- R3L (p.Arg3Leu), rs2116860662, ClinGen CA368931647, cosmic curated COSV10740, ClinVar RCV002008009, REVEL 0.11, MetaLR 0.04, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- S4N (p.Ser4Asn), gnomAD rs1394903450
- S4R (p.Ser4Arg), TOPMed rs1797174926, REVEL 0.03, MetaLR 0.03
- S4T (p.Ser4Thr), gnomAD rs1394903450, MetaLR 0.04, MetaSVM -1.07
- G5S (p.Gly5Ser), rs766288841, ClinGen CA4422745, ClinVar RCV003043743, ExAC rs766288841, REVEL 0.04, MetaLR 0.02, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- G5V (p.Gly5Val), TOPMed rs1797174683, gnomAD rs1797174683, REVEL 0.02, MetaLR 0.03
- W6* (p.Trp6Ter), TOPMed rs1797174443
- W6C (p.Trp6Cys), TOPMed rs1797174443, REVEL 0.07, MetaLR 0.04
- W6R (p.Trp6Arg), ExAC rs758270576, gnomAD rs758270576, REVEL 0.07, MetaLR 0.03
- W6S (p.Trp6Ser), Ensembl rs1563128115, MetaLR 0.03, MetaSVM -1.05
- A7S (p.Ala7Ser), ExAC rs750179737, TOPMed rs750179737, gnomAD rs750179737, REVEL 0.06, MetaLR 0.05, Uncertain significance, Inborn genetic diseases
- A7T (p.Ala7Thr), ExAC rs750179737, TOPMed rs750179737, gnomAD rs750179737, REVEL 0.07, MetaLR 0.05
- R8G (p.Arg8Gly), rs1470522542, ClinGen CA368931620, ClinVar RCV000557579, TOPMed rs1470522542, REVEL 0.08, MetaLR 0.05, Likely benign, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- R8L (p.Arg8Leu), ExAC rs765261158, TOPMed rs765261158, gnomAD rs765261158, MetaLR 0.05, MetaSVM -0.98, Uncertain significance, Inborn genetic diseases
- R8P (p.Arg8Pro), ExAC rs765261158, TOPMed rs765261158, gnomAD rs765261158, REVEL 0.05, MetaLR 0.05, Likely benign
- R8Q (p.Arg8Gln), rs765261158, ClinGen CA4422742, cosmic curated COSV58987, ClinVar RCV001162132, REVEL 0.06, MetaLR 0.04, Conflicting interpretations, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- R8W (p.Arg8Trp), rs1470522542, ClinGen CA368931619, ClinVar RCV003798790, TOPMed rs1470522542, REVEL 0.11, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- Q9E (p.Gln9Glu), rs1797174077, ClinGen CA368931615, ClinVar RCV001239697, Ensembl rs1797174077, AlphaMissense 0.08, MetaLR 0.02, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- Q9P (p.Gln9Pro), rs115165703, ClinGen CA148341, ClinVar RCV000081229, ClinVar RCV000264190, REVEL 0.04, MetaLR 0.00, Benign/Likely benign, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7; not specified
- Q9R (p.Gln9Arg), rs115165703, ClinGen CA4422741, ClinVar RCV001368450, 1000Genomes rs115165703, REVEL 0.06, MetaLR 0.02, Likely benign, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- T10A (p.Thr10Ala), rs1584425962, ClinGen CA368931609, ClinVar RCV002958541, gnomAD rs1584425962, REVEL 0.02, MetaLR 0.03, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- T10I (p.Thr10Ile), TOPMed rs1403460416, gnomAD rs1403460416, REVEL 0.04, MetaLR 0.04
- T10S (p.Thr10Ser), rs1584425962, ClinGen CA368931608, ClinVar RCV001245987, gnomAD rs1584425962, REVEL 0.05, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- F11C (p.Phe11Cys), rs764120718, ClinGen CA207022, ClinVar RCV000193495, ClinVar RCV002517125, REVEL 0.05, MetaLR 0.03, Uncertain significance, not specified; Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- F11L (p.Phe11Leu), TOPMed rs1258431125, gnomAD rs1258431125, REVEL 0.04, MetaLR 0.03, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- F11V (p.Phe11Val), TOPMed rs1258431125, gnomAD rs1258431125, REVEL 0.08, MetaLR 0.03
- L12F (p.Leu12Phe), rs760894850, ClinGen CA4422740, ClinVar RCV002015555, ExAC rs760894850, REVEL 0.02, MetaLR 0.04, Likely benign, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- L12R (p.Leu12Arg), rs2484918399, ClinGen CA368931593, ClinVar RCV003026246, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- A14G (p.Ala14Gly), TOPMed rs1224049310, gnomAD rs1224049310, REVEL 0.06, MetaLR 0.03, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- A14S (p.Ala14Ser), rs147551940, ClinGen CA4422737, ClinVar RCV001339844, ClinVar RCV004719140, REVEL 0.05, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7; not provided
- A14T (p.Ala14Thr), rs147551940, ClinGen CA4422738, ClinVar RCV001302592, ESP rs147551940, REVEL 0.05, MetaLR 0.04, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- A14V (p.Ala14Val), TOPMed rs1224049310, gnomAD rs1224049310, REVEL 0.04, MetaLR 0.03, Uncertain significance, Inborn genetic diseases
- L16F (p.Leu16Phe), rs1563128080, ClinGen CA368931572, ClinVar RCV002466992, ClinVar RCV003331371, REVEL 0.03, MetaLR 0.04, Uncertain significance, not specified; not provided
- L16S (p.Leu16Ser), TOPMed rs1797173305
- G18V (p.Gly18Val), rs1352208816, ClinGen CA368931561, ClinVar RCV002299843, AlphaMissense 0.40, MetaLR 0.08, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- G18E (p.Gly18Glu), rs1352208816, gnomAD rs1352208816, REVEL 0.17, AlphaMissense 0.40, Uncertain significance, not provided
- A19E (p.Ala19Glu), 1000Genomes rs557229008, ExAC rs557229008, gnomAD rs557229008
- A19G (p.Ala19Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A19S (p.Ala19Ser), rs774554247, ClinGen CA4422736, cosmic curated COSV59042, ClinVar RCV003780074, AlphaMissense 0.11, MetaLR 0.07, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- A19V (p.Ala19Val), cosmic curated COSV59005, 1000Genomes rs557229008, ExAC rs557229008, gnomAD rs557229008, REVEL 0.15, MetaLR 0.09, Likely benign, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- T20M (p.Thr20Met), rs145135688, ClinGen CA4422734, cosmic curated COSV10063, ClinVar RCV000653030, REVEL 0.04, MetaLR 0.03, Conflicting interpretations, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome; not provided
- L21P (p.Leu21Pro), rs1584425842, ClinGen CA368931547, ClinVar RCV003784473, Ensembl rs1584425842, REVEL 0.24, MetaLR 0.05, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- L21V (p.Leu21Val), Ensembl rs1797172669, REVEL 0.04, MetaLR 0.04, Likely benign
- R22K (p.Arg22Lys), rs139532757, ClinGen CA164084536, ClinVar RCV001300053, ClinVar RCV003485704, REVEL 0.06, MetaLR 0.03, Conflicting interpretations, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- R22M (p.Arg22Met), rs139532757, ClinGen CA4422731, ClinVar RCV001065378, ClinVar RCV001557478, REVEL 0.08, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7; Inborn genetic disea
- A23E (p.Ala23Glu), ESP rs370745351, ExAC rs370745351, gnomAD rs370745351, REVEL 0.21, MetaLR 0.04, Likely benign
- A23T (p.Ala23Thr), rs2484918249, ClinGen CA368931541, ClinVar RCV003093778, REVEL 0.03, MetaLR 0.04, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- A23V (p.Ala23Val), rs370745351, ClinGen CA4422730, cosmic curated COSV10063, ClinVar RCV003782409, REVEL 0.02, MetaLR 0.02, Likely benign, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- R24G (p.Arg24Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R24P (p.Arg24Pro), TOPMed rs1797172242, gnomAD rs1797172242, REVEL 0.18, MetaLR 0.05
- A25S (p.Ala25Ser), Ensembl rs1214320410, MetaLR 0.03, MetaSVM -1.05
- A25V (p.Ala25Val), rs757957218, ClinGen CA4422728, ClinVar RCV001336778, ClinVar RCV003770865, REVEL 0.03, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- A26T (p.Ala26Thr), Ensembl rs956489179, REVEL 0.04, MetaLR 0.03
- A26V (p.Ala26Val), rs144557847, ClinGen CA238806, cosmic curated COSV58987, ClinVar RCV000173363, REVEL 0.07, MetaLR 0.03, Conflicting interpretations, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7; not specified
- A27T (p.Ala27Thr), rs2116860341, ClinGen CA368931521, ClinVar RCV001989313, Ensembl rs2116860341, REVEL 0.04, MetaLR 0.03, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- A27V (p.Ala27Val), cosmic curated COSV59027, Ensembl rs1187486099, MetaLR 0.02, MetaSVM -0.98
- G28A (p.Gly28Ala), rs757218424, ExAC rs757218424, gnomAD rs757218424, REVEL 0.08, MetaLR 0.04, Variant assessed as somatic; moderate impact.
- Y29C (p.Tyr29Cys), ExAC rs753710957, gnomAD rs753710957, REVEL 0.05, MetaLR 0.04, Conflicting interpretations, not specified; Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- Y29H (p.Tyr29His), gnomAD rs1216023136, REVEL 0.05, MetaLR 0.04
- Y30C (p.Tyr30Cys), rs2484918138, ClinGen CA368931500, ClinVar RCV003807540, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- Y30H (p.Tyr30His), ExAC rs764175823, TOPMed rs764175823, gnomAD rs764175823, REVEL 0.13, MetaLR 0.04, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- Y30N (p.Tyr30Asn), rs764175823, ClinGen CA368931503, ClinVar RCV001038886, ClinVar RCV004958373, REVEL 0.12, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7; Inborn genetic disea
- P31L (p.Pro31Leu), rs759623259, ClinGen CA4422721, ClinVar RCV001340256, ExAC rs759623259, REVEL 0.36, MetaLR 0.11, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- P31R (p.Pro31Arg), ExAC rs759623259, TOPMed rs759623259, gnomAD rs759623259, REVEL 0.42, MetaLR 0.11, Uncertain significance
- P31S (p.Pro31Ser), rs752774374, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, ExAC rs752774374, REVEL 0.38, MetaLR 0.11, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- P31T (p.Pro31Thr), ExAC rs752774374, gnomAD rs752774374, REVEL 0.33, MetaLR 0.11
- R32A (p.Arg32Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R32C (p.Arg32Cys), gnomAD rs1364193123, REVEL 0.20, MetaLR 0.03
- R32H (p.Arg32His), cosmic curated COSV58995, gnomAD rs1270595402, MetaLR 0.07, MetaSVM -1.02, Uncertain significance, Inborn genetic diseases
- R32S (p.Arg32Ser), gnomAD rs1364193123, REVEL 0.20, MetaLR 0.03
- S34* (p.Ser34Ter), NCI-TCGA Cosmic COSV5901, Variant assessed as somatic; high impact.
- S34L (p.Ser34Leu), cosmic curated COSV59018, TOPMed rs1255586221
- S34P (p.Ser34Pro), NCI-TCGA Cosmic COSV5900, cosmic curated COSV59004, Variant assessed as somatic; moderate impact.
- P35S (p.Pro35Ser), rs2116860248, ClinGen CA2573141417, ClinVar RCV001948119, Ensembl rs2116860248, REVEL 0.37, MetaLR 0.14, Uncertain significance, Inborn genetic diseases
- F37I (p.Phe37Ile), TOPMed rs1797170618, REVEL 0.35, MetaLR 0.09
- F37L (p.Phe37Leu), rs1797170618, ClinGen CA368931459, ClinVar RCV003046415, REVEL 0.29, MetaLR 0.07, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- F38S (p.Phe38Ser), NCI-TCGA Cosmic COSV5900, cosmic curated COSV59007, MetaLR 0.10, MetaSVM -0.94, Variant assessed as somatic; moderate impact.
- F38Y (p.Phe38Tyr), rs149715692, ClinGen CA4422715, ClinVar RCV000377477, ClinVar RCV001039282, REVEL 0.27, MetaLR 0.10, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7; Inborn genetic disea
- H42Y (p.His42Tyr), rs1376719484, ClinGen CA368931424, ClinVar RCV003781977, TOPMed rs1376719484, REVEL 0.30, MetaLR 0.08, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- H43N (p.His43Asn), rs369522512, ClinGen CA4422713, ClinVar RCV000689982, ESP rs369522512, REVEL 0.27, MetaLR 0.10, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- H43Q (p.His43Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H43Y (p.His43Tyr), ESP rs369522512, ExAC rs369522512, TOPMed rs369522512, gnomAD rs369522512, Uncertain significance
- G44E (p.Gly44Glu), Ensembl rs1797169982
- G44R (p.Gly44Arg), ESP rs375165806, TOPMed rs375165806, gnomAD rs375165806, REVEL 0.38, MetaLR 0.10
- G44W (p.Gly44Trp), cosmic curated COSV10063, ESP rs375165806, TOPMed rs375165806, gnomAD rs375165806
- L46M (p.Leu46Met), cosmic curated COSV59028, gnomAD rs1400698002
- E47K (p.Glu47Lys), rs139648092, ClinGen CA222810, cosmic curated COSV99067, ClinVar RCV000317927, REVEL 0.05, MetaLR 0.04, Conflicting interpretations, Inborn genetic diseases; Norman-Roberts syndrome; Familial temporal lobe epileps
- G48R (p.Gly48Arg), gnomAD rs1476609646, REVEL 0.31, MetaLR 0.10
- D49G (p.Asp49Gly), Ensembl rs1311750528, MetaLR 0.04, MetaSVM -1.04
- D49N (p.Asp49Asn), ExAC rs745472493, gnomAD rs745472493, REVEL 0.13, MetaLR 0.05
- G50R (p.Gly50Arg), NCI-TCGA Cosmic COSV5903, cosmic curated COSV59036, Variant assessed as somatic; moderate impact.
- Q52E (p.Gln52Glu), ESP rs372475867, ExAC rs372475867, TOPMed rs372475867, gnomAD rs372475867, REVEL 0.10, MetaLR 0.03
- Q52H (p.Gln52His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G53D (p.Gly53Asp), NCI-TCGA TCGA novel, MetaLR 0.21, MetaSVM -0.66, Variant assessed as somatic; moderate impact.
- E54* (p.Glu54Ter), NCI-TCGA TCGA novel, CADD 37.00, Variant assessed as somatic; high impact.
- E54A (p.Glu54Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E54D (p.Glu54Asp), Ensembl rs1797169282, REVEL 0.14, MetaLR 0.04
- E54G (p.Glu54Gly), TOPMed rs1797169331, gnomAD rs1797169331, REVEL 0.29, MetaLR 0.07
- E54K (p.Glu54Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V55A (p.Val55Ala), rs1285117765, ClinGen CA368931335, ClinVar RCV002813861, TOPMed rs1285117765, AlphaMissense 0.71, MetaLR 0.10, Uncertain significance, Inborn genetic diseases
- V55L (p.Val55Leu), rs753619762, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, ExAC rs753619762, REVEL 0.33, MetaLR 0.10, Uncertain significance
- V55M (p.Val55Met), rs753619762, ClinGen CA368931336, ClinVar RCV001294460, ExAC rs753619762, REVEL 0.33, MetaLR 0.10, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- L56F (p.Leu56Phe), rs777758550, ClinGen CA4422708, ClinVar RCV001953306, ExAC rs777758550, REVEL 0.32, MetaLR 0.10, Likely benign, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- L56V (p.Leu56Val), ExAC rs777758550, gnomAD rs777758550, REVEL 0.34, MetaLR 0.10, Likely benign
- S58F (p.Ser58Phe), rs1797168998, ClinGen CA368931315, cosmic curated COSV58984, ClinVar RCV001360340, REVEL 0.26, MetaLR 0.07, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- L59M (p.Leu59Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L59P (p.Leu59Pro), rs1466636409, ClinGen CA368931311, ClinVar RCV001870099, gnomAD rs1466636409, REVEL 0.57, MetaLR 0.19, Likely benign, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- H60R (p.His60Arg), rs1584425634, ClinGen CA368931305, ClinVar RCV000812208, Ensembl rs1584425634, REVEL 0.20, MetaLR 0.03, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- I61L (p.Ile61Leu), TOPMed rs1373111164, gnomAD rs1373111164, MetaLR 0.03, MetaSVM -1.07
- I61V (p.Ile61Val), TOPMed rs1373111164, gnomAD rs1373111164, REVEL 0.07, MetaLR 0.03
- A62T (p.Ala62Thr), rs1238589028, NCI-TCGA Cosmic COSV5902, cosmic curated COSV59022, TOPMed rs1238589028, REVEL 0.06, MetaLR 0.05, Variant assessed as somatic; moderate impact.
- A62V (p.Ala62Val), rs756018749, ClinGen CA4422707, ClinVar RCV000432487, ClinVar RCV001865400, REVEL 0.29, MetaLR 0.05, Conflicting interpretations, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7; not provided
- G63C (p.Gly63Cys), rs752841369, ClinGen CA4422706, ClinVar RCV002711206, ExAC rs752841369, AlphaMissense 0.18, MetaLR 0.17, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- G63D (p.Gly63Asp), rs1085307660, ClinGen CA368931287, ClinVar RCV000489323, TOPMed rs1085307660, REVEL 0.32, MetaLR 0.19, Uncertain significance, not provided
- G63S (p.Gly63Ser), ExAC rs752841369, TOPMed rs752841369, gnomAD rs752841369, REVEL 0.28, AlphaMissense 0.18, Uncertain significance
- N64S (p.Asn64Ser), rs759805907, ClinGen CA4422704, ClinVar RCV003806050, ExAC rs759805907, REVEL 0.03, MetaLR 0.04, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- P65H (p.Pro65His), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, Variant assessed as somatic; moderate impact.
- P65R (p.Pro65Arg), gnomAD rs1439311948, REVEL 0.46, MetaLR 0.15
- P65S (p.Pro65Ser), rs1797168163, ClinGen CA368931275, ClinVar RCV001044206, Ensembl rs1797168163, AlphaMissense 0.80, MetaLR 0.15, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- T66A (p.Thr66Ala), rs751673305, ClinGen CA164084380, ClinVar RCV001987688, ClinVar RCV005473043, REVEL 0.08, MetaLR 0.03, Uncertain significance, Inborn genetic diseases; Norman-Roberts syndrome; Familial temporal lobe epileps
- T66P (p.Thr66Pro), ExAC rs751673305, TOPMed rs751673305, REVEL 0.13, MetaLR 0.04, Uncertain significance
- Y67C (p.Tyr67Cys), ExAC rs763477584, gnomAD rs763477584, REVEL 0.07, MetaLR 0.03
- Y67H (p.Tyr67His), ExAC rs766692886, gnomAD rs766692886
- Y67T (p.Tyr67Thr), NCI-TCGA TCGA novel, MetaLR 0.02, MetaSVM -1.04, Variant assessed as somatic; high impact.
- Y68* (p.Tyr68Ter), rs2484917661, ClinGen CA368931254, ClinVar RCV002464044, Pathogenic
- Y68C (p.Tyr68Cys), gnomAD rs1797167752, REVEL 0.51, MetaLR 0.26
- V69I (p.Val69Ile), rs2484917656, ClinGen CA368931253, ClinVar RCV002303806, REVEL 0.06, MetaLR 0.05, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- P70S (p.Pro70Ser), rs773680003, ExAC rs773680003, gnomAD rs773680003, REVEL 0.24, MetaLR 0.19, Uncertain significance
- P70T (p.Pro70Thr), rs773680003, ClinGen CA4422700, ClinVar RCV001216705, ExAC rs773680003, REVEL 0.36, MetaLR 0.25, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- G71A (p.Gly71Ala), ExAC rs762361761, TOPMed rs762361761, gnomAD rs762361761, REVEL 0.33, MetaLR 0.18
- G71E (p.Gly71Glu), ExAC rs762361761, TOPMed rs762361761, gnomAD rs762361761, REVEL 0.32, MetaLR 0.16
- G71R (p.Gly71Arg), rs976170143, ClinGen CA164084366, ClinVar RCV002741065, ClinVar RCV005473231, REVEL 0.36, MetaLR 0.19, Conflicting interpretations, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome; Inborn genetic disea
- Q72E (p.Gln72Glu), rs775097828, ClinGen CA4422697, ClinVar RCV001365276, ExAC rs775097828, REVEL 0.14, MetaLR 0.04, Likely benign, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- Q72H (p.Gln72His), ExAC rs771418741, TOPMed rs771418741, gnomAD rs771418741, REVEL 0.07, MetaLR 0.04
- Q72R (p.Gln72Arg), TOPMed rs924080257, gnomAD rs924080257, REVEL 0.14, MetaLR 0.05
- E73A (p.Glu73Ala), NCI-TCGA Cosmic COSV5900, cosmic curated COSV59002, Variant assessed as somatic; moderate impact.
- E73K (p.Glu73Lys), NCI-TCGA Cosmic COSV1006, NCI-TCGA Cosmic COSV5901, cosmic curated COSV59017, REVEL 0.34, MetaLR 0.07, Variant assessed as somatic; moderate impact.
- E73Q (p.Glu73Gln), Ensembl rs1382025988, REVEL 0.32, MetaLR 0.11, Uncertain significance, Norman-Roberts syndrome
- E73V (p.Glu73Val), rs2484917597, ClinGen CA368931228, ClinVar RCV004443866, Uncertain significance, Inborn genetic diseases
- H75L (p.His75Leu), rs770570216, ClinGen CA368931215, ClinVar RCV001892914, ExAC rs770570216, REVEL 0.14, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- H75N (p.His75Asn), rs555377051, ClinGen CA4422694, ClinVar RCV001056156, 1000Genomes rs555377051, REVEL 0.14, AlphaMissense 0.10, Likely benign, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- H75R (p.His75Arg), rs770570216, ClinGen CA4422693, ClinVar RCV001059638, ExAC rs770570216, REVEL 0.18, MetaLR 0.03, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- H75Y (p.His75Tyr), rs555377051, ClinGen CA10627845, ClinVar RCV000262788, 1000Genomes rs555377051, AlphaMissense 0.10, MetaLR 0.03, Uncertain significance, Norman-Roberts syndrome
- T77I (p.Thr77Ile), rs150587706, ClinGen CA4422647, ClinVar RCV001727419, ESP rs150587706, REVEL 0.38, MetaLR 0.12, Uncertain significance, not provided
- I78T (p.Ile78Thr), rs1795501891, ClinGen CA368931183, cosmic curated COSV10740, ClinVar RCV002815100, AlphaMissense 0.98, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- I78V (p.Ile78Val), rs768499951, ClinGen CA4422646, ClinVar RCV001065267, ExAC rs768499951, REVEL 0.06, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- S81N (p.Ser81Asn), gnomAD rs1345826603, REVEL 0.18, MetaLR 0.10
- S81R (p.Ser81Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T82I (p.Thr82Ile), rs368049573, ClinGen CA4422645, cosmic curated COSV59016, ClinVar RCV001309004, REVEL 0.31, MetaLR 0.10, Likely benign, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- T82N (p.Thr82Asn), rs368049573, ClinGen CA368931155, ClinVar RCV001300498, ESP rs368049573, REVEL 0.23, MetaLR 0.10, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- F84I (p.Phe84Ile), NCI-TCGA TCGA novel, MetaLR 0.09, MetaSVM -1.07, Variant assessed as somatic; moderate impact.
- F84Y (p.Phe84Tyr), ExAC rs772223037, gnomAD rs772223037, REVEL 0.30, MetaLR 0.11
- G86C (p.Gly86Cys), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, Variant assessed as somatic; moderate impact.
- G86D (p.Gly86Asp), NCI-TCGA Cosmic COSV1006, NCI-TCGA Cosmic COSV5903, cosmic curated COSV59036, MetaLR 0.12, MetaSVM -0.99, Uncertain significance, Inborn genetic diseases
- G86S (p.Gly86Ser), cosmic curated COSV10591, TOPMed rs1795501414, REVEL 0.25, MetaLR 0.11
- G86V (p.Gly86Val), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, NCI-TCGA Cosmic COSV5903, REVEL 0.41, MetaLR 0.12, Variant assessed as somatic; moderate impact.
- L87* (p.Leu87Ter), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, Variant assessed as somatic; high impact.
- L87F (p.Leu87Phe), rs779347175, ClinGen CA4422642, ClinVar RCV001905465, ExAC rs779347175, REVEL 0.29, MetaLR 0.04, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- L87W (p.Leu87Trp), Ensembl rs1795501358, MetaLR 0.11, MetaSVM -0.91
- V89L (p.Val89Leu), rs778154915, ClinGen CA368931113, ClinVar RCV001046902, ExAC rs778154915, REVEL 0.19, MetaLR 0.05, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- V89M (p.Val89Met), ExAC rs778154915, gnomAD rs778154915, Uncertain significance
- L92I (p.Leu92Ile), TOPMed rs1365812675
- Y93C (p.Tyr93Cys), rs2484778936, ClinGen CA368931086, ClinVar RCV002843335, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- T94K (p.Thr94Lys), TOPMed rs1795500741, MetaLR 0.07, MetaSVM -1.03
- S95A (p.Ser95Ala), gnomAD rs1160469188, REVEL 0.20, MetaLR 0.07
- S95C (p.Ser95Cys), ExAC rs767995779, gnomAD rs767995779
- S95F (p.Ser95Phe), ExAC rs767995779, gnomAD rs767995779, REVEL 0.30, MetaLR 0.11
- T96A (p.Thr96Ala), rs564088219, ClinGen CA164029205, ClinVar RCV001319644, 1000Genomes rs564088219, REVEL 0.16, MetaLR 0.06, Uncertain significance, Familial temporal lobe epilepsy 7; Norman-Roberts syndrome
- S97G (p.Ser97Gly), rs1795500406, ClinGen CA368931065, ClinVar RCV003797642, TOPMed rs1795500406, REVEL 0.05, MetaLR 0.03, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- S97R (p.Ser97Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S97T (p.Ser97Thr), Ensembl rs1795500353, MetaLR 0.05, MetaSVM -1.05
- V98A (p.Val98Ala), rs1471699014, ClinGen CA368931053, ClinVar RCV000762476, ClinVar RCV001855955, REVEL 0.03, MetaLR 0.02, Uncertain significance, Inborn genetic diseases; Familial temporal lobe epilepsy 7; Norman-Roberts syndr
- V98I (p.Val98Ile), rs1795500299, ClinGen CA368931058, ClinVar RCV003812550, REVEL 0.03, MetaLR 0.02, Uncertain significance, Norman-Roberts syndrome; Familial temporal lobe epilepsy 7
- V98L (p.Val98Leu), Ensembl rs1795500299, REVEL 0.03, MetaLR 0.02
- Q99* (p.Gln99Ter), ExAC rs762514238, TOPMed rs762514238, gnomAD rs762514238
Public RELN analysis runs
- RELN analysis run — RELN (4,727 variants) — completed 2026-08-20