CREB3L3 — 319 ClinVar variants
All ClinVar germline CREB3L3 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 133 flagged for review →
10 Pathogenic · 4 Pathogenic/Likely pathogenic · 4 Likely pathogenic · 12 Conflicting · 30 Benign · 12 Benign/Likely benign · 96 Likely benign · 151 Uncertain significance
Full CREB3L3 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 133
Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.
Predictors agree, ClinVar conflicts 8
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
- CREB3L3 p.Arg103His Conflicting Single submitter
- CREB3L3 p.Arg451Cys Conflicting Single submitter
-
CREB3L3 p.Glu240Lys
Conflicting
Single submitter
episodic kinesigenic dyskinesia 1
- CREB3L3 p.Glu380Lys Conflicting Single submitter
- CREB3L3 p.Gly400Arg Conflicting Single submitter
- CREB3L3 p.Pro118Ala Conflicting Single submitter
- CREB3L3 p.Pro94Thr Conflicting Single submitter
- CREB3L3 p.Thr3Met Conflicting Single submitter
Predictors lean, ClinVar uncertain 111
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
- CREB3L3 p.Ala111Thr Uncertain significance Multiple submitters
- CREB3L3 p.Ala167Thr Uncertain significance Multiple submitters
- CREB3L3 p.Ala442Val Uncertain significance Multiple submitters
- CREB3L3 p.Arg248Cys Uncertain significance Multiple submitters
- CREB3L3 p.Arg32Gln Uncertain significance Multiple submitters
- CREB3L3 p.Cys210Arg Uncertain significance Multiple submitters
- CREB3L3 p.Glu387Gln Uncertain significance Multiple submitters
- CREB3L3 p.Gly105Glu Uncertain significance Multiple submitters
- CREB3L3 p.Gly121Glu Uncertain significance Multiple submitters
- CREB3L3 p.Gly159Glu Uncertain significance Multiple submitters
- CREB3L3 p.Gly321Asp Uncertain significance Multiple submitters
- CREB3L3 p.Gly43Cys Uncertain significance Multiple submitters
- CREB3L3 p.His196Tyr Uncertain significance Multiple submitters
- CREB3L3 p.Leu26Pro Uncertain significance Multiple submitters
- CREB3L3 p.Pro166Leu Uncertain significance Multiple submitters
- CREB3L3 p.Ala11Val Uncertain significance Single submitter
- CREB3L3 p.Ala14Asp Uncertain significance Single submitter
- CREB3L3 p.Ala257Pro Uncertain significance Single submitter
- CREB3L3 p.Ala280Pro Uncertain significance Single submitter
- CREB3L3 p.Ala373Gly Uncertain significance Single submitter
- CREB3L3 p.Ala381Ser Uncertain significance Single submitter
- CREB3L3 p.Ala381Val Uncertain significance Single submitter
- CREB3L3 p.Ala428Thr Uncertain significance Single submitter
- CREB3L3 p.Ala436Thr Uncertain significance Single submitter
- CREB3L3 p.Ala452Glu Uncertain significance Single submitter
- CREB3L3 p.Ala456Val Uncertain significance Single submitter
- CREB3L3 p.Ala457Val Uncertain significance Single submitter
- CREB3L3 p.Arg103Cys Uncertain significance Single submitter
- CREB3L3 p.Arg103Leu Uncertain significance Single submitter
- CREB3L3 p.Arg175Pro Uncertain significance Single submitter
- CREB3L3 p.Arg204Gln Uncertain significance Single submitter
- CREB3L3 p.Arg242Pro Uncertain significance Single submitter
- CREB3L3 p.Arg248His Uncertain significance Single submitter
- CREB3L3 p.Arg252Gln Uncertain significance Single submitter
- CREB3L3 p.Arg274Trp Uncertain significance Single submitter
- CREB3L3 p.Arg357Gln Uncertain significance Single submitter
- CREB3L3 p.Arg370His Uncertain significance Single submitter
- CREB3L3 p.Arg385Gly Uncertain significance Single submitter
- CREB3L3 p.Arg426Lys Uncertain significance Single submitter
- CREB3L3 p.Arg451His Uncertain significance Single submitter
- CREB3L3 p.Asn2Asp Uncertain significance Single submitter
- CREB3L3 p.Asn345Lys Uncertain significance Single submitter
- CREB3L3 p.Asn413Lys Uncertain significance Single submitter
- CREB3L3 p.Asn420Ser Uncertain significance Single submitter
- CREB3L3 p.Asp171His Uncertain significance Single submitter
- CREB3L3 p.Asp191Glu Uncertain significance Single submitter
- CREB3L3 p.Asp21Asn Uncertain significance Single submitter
- CREB3L3 p.Asp374Val Uncertain significance Single submitter
- CREB3L3 p.Asp402Glu Uncertain significance Single submitter
- CREB3L3 p.Asp407Gly Uncertain significance Single submitter
- CREB3L3 p.Asp62Asn Uncertain significance Single submitter
- CREB3L3 p.Asp72Tyr Uncertain significance Single submitter
- CREB3L3 p.Asp96Asn Uncertain significance Single submitter
-
CREB3L3 p.Cys162Tyr
Uncertain significance
Single submitter
hypertriglyceridemia 2
- CREB3L3 p.Cys176Phe Uncertain significance Single submitter
- CREB3L3 p.Cys210Ser Uncertain significance Single submitter
- CREB3L3 p.Gln312Arg Uncertain significance Single submitter
- CREB3L3 p.Glu259Gln Uncertain significance Single submitter
- CREB3L3 p.Glu348Lys Uncertain significance Single submitter
- CREB3L3 p.Glu380Asp Uncertain significance Single submitter
- CREB3L3 p.Glu44Gly Uncertain significance Single submitter
- CREB3L3 p.Glu455Gln Uncertain significance Single submitter
- CREB3L3 p.Gly198Arg Uncertain significance Single submitter
- CREB3L3 p.Gly378Arg Uncertain significance Single submitter
- CREB3L3 p.Gly404Ser Uncertain significance Single submitter
- CREB3L3 p.Gly431Val Uncertain significance Single submitter
- CREB3L3 p.Gly47Val Uncertain significance Single submitter
- CREB3L3 p.Gly84Asp Uncertain significance Single submitter
- CREB3L3 p.His114Arg Uncertain significance Single submitter
- CREB3L3 p.His114Leu Uncertain significance Single submitter
- CREB3L3 p.Ile20Asn Uncertain significance Single submitter
- CREB3L3 p.Ile247Phe Uncertain significance Single submitter
- CREB3L3 p.Ile247Val Uncertain significance Single submitter
- CREB3L3 p.Ile309Thr Uncertain significance Single submitter
- CREB3L3 p.Ile339Val Uncertain significance Single submitter
- CREB3L3 p.Leu124Phe Uncertain significance Single submitter
- CREB3L3 p.Leu183Pro Uncertain significance Single submitter
- CREB3L3 p.Leu215Phe Uncertain significance Single submitter
- CREB3L3 p.Lys254Asn Uncertain significance Single submitter
- CREB3L3 p.Met17Val Uncertain significance Single submitter
- CREB3L3 p.Met275Arg Uncertain significance Single submitter
- CREB3L3 p.Pro115Ala Uncertain significance Single submitter
- CREB3L3 p.Pro115His Uncertain significance Single submitter
- CREB3L3 p.Pro118Ser Uncertain significance Single submitter
- CREB3L3 p.Pro118Thr Uncertain significance Single submitter
- CREB3L3 p.Pro144Leu Uncertain significance Single submitter
- CREB3L3 p.Pro19Ser Uncertain significance Single submitter
- CREB3L3 p.Pro386Thr Uncertain significance Single submitter
- CREB3L3 p.Pro445Gln Uncertain significance Single submitter
- CREB3L3 p.Pro445Leu Uncertain significance Single submitter
- CREB3L3 p.Pro445Ser Uncertain significance Single submitter
- CREB3L3 p.Pro78Arg Uncertain significance Single submitter
- CREB3L3 p.Ser12Phe Uncertain significance Single submitter
- CREB3L3 p.Ser156Ile Uncertain significance Single submitter
- CREB3L3 p.Ser186Leu Uncertain significance Single submitter
- CREB3L3 p.Ser189Asn Uncertain significance Single submitter
- CREB3L3 p.Ser22Arg Uncertain significance Single submitter
- CREB3L3 p.Ser256Leu Uncertain significance Single submitter
- CREB3L3 p.Ser260Asn Uncertain significance Single submitter
- CREB3L3 p.Ser330Phe Uncertain significance Single submitter
- CREB3L3 p.Ser360Phe Uncertain significance Single submitter
- CREB3L3 p.Ser360Tyr Uncertain significance Single submitter
- CREB3L3 p.Ser369Tyr Uncertain significance Single submitter
- CREB3L3 p.Ser65Arg Uncertain significance Single submitter
- CREB3L3 p.Thr136Pro Uncertain significance Single submitter
- CREB3L3 p.Thr314Ala Uncertain significance Single submitter
- CREB3L3 p.Trp403Ser Uncertain significance Single submitter
- CREB3L3 p.Trp80Gly Uncertain significance Single submitter
- CREB3L3 p.Val140Glu Uncertain significance Single submitter
- CREB3L3 p.Val371Met Uncertain significance Single submitter
- CREB3L3 p.Val40Met Uncertain significance Single submitter
Predictors split 14
The independent predictors disagree with each other — read with care.
- CREB3L3 p.Leu28Arg Uncertain significance Multiple submitters
- CREB3L3 p.Arg370Cys Uncertain significance Single submitter
- CREB3L3 p.Asp31Gly Uncertain significance Single submitter
- CREB3L3 p.Asp34Gly Uncertain significance Single submitter
- CREB3L3 p.Glu293Lys Uncertain significance Single submitter
- CREB3L3 p.Glu301Lys Uncertain significance Single submitter
- CREB3L3 p.Glu460Lys Uncertain significance Single submitter
- CREB3L3 p.Ile150Thr Likely benign Single submitter
- CREB3L3 p.Leu152Pro Uncertain significance Single submitter
- CREB3L3 p.Leu303Val Uncertain significance Single submitter
- CREB3L3 p.Phe342Leu Uncertain significance Single submitter
- CREB3L3 p.Phe359Leu Uncertain significance Single submitter
- CREB3L3 p.Trp155Gly Uncertain significance Single submitter
- CREB3L3 p.Val289Leu Uncertain significance Single submitter
All CREB3L3 variants
Pathogenic 10
- p.Arg103fs Single submitter
- p.Arg160fs Single submitter
- p.Gln193Ter Single submitter
- p.Gln211fs Single submitter
- p.Glu153Ter Single submitter
- p.Glu44Ter Single submitter
- p.Ser81fs Single submitter
- p.Tyr201Ter Single submitter
- p.Tyr239Ter Single submitter
- p.Cys123fs No assertion criteria hypertriglyceridemia 2
Pathogenic/Likely pathogenic 4
- p.Arg175Ter Multiple submitters
- p.Arg204Ter Multiple submitters
- p.Arg242Ter Multiple submitters hypertriglyceridemia 2
- p.Trp46Ter Multiple submitters hypertriglyceridemia 2
Likely pathogenic 4
- c.577-1G>A Single submitter
- c.577-2A>G Single submitter
- c.891-2A>G Single submitter
- p.Arg242fs Single submitter hypertriglyceridemia 2
Conflicting classifications of pathogenicity 12
- c.27+2T>C Single submitter
- p.Arg103His Single submitter ⚠
- p.Arg392Ter Single submitter hypertriglyceridemia 2
- p.Arg451Cys Single submitter ⚠
- p.Glu240Lys Single submitter episodic kinesigenic dyskinesia 1 ⚠
- p.Glu380Lys Single submitter ⚠
- p.Gly400Arg Single submitter ⚠
- p.Ile247fs Single submitter hypertriglyceridemia 2
- p.Lys245fs Single submitter hypertriglyceridemia 2
- p.Pro118Ala Single submitter ⚠
- p.Pro94Thr Single submitter ⚠
- p.Thr3Met Single submitter ⚠
Benign 30
- c.157-111G>A Multiple submitters
- c.157-123C>T Multiple submitters
- c.157-151G>A Multiple submitters
- c.157-53C>G Multiple submitters
- c.27+85T>C Multiple submitters
- c.28-50G>A Multiple submitters
- c.458-152C>T Multiple submitters
- c.458-98C>G Multiple submitters
- c.576+94A>G Multiple submitters
- c.577-26C>T Multiple submitters
- c.822-139G>A Multiple submitters
- c.822-16G>A Multiple submitters
- c.890+173G>A Multiple submitters
- c.891-14C>T Multiple submitters hypertriglyceridemia 2
- c.-86G>A Multiple submitters
- c.*6G>A Multiple submitters
- p.Ala14= Multiple submitters
- p.Gly105Arg Multiple submitters hypertriglyceridemia 2
- p.Ile268= Multiple submitters
- p.Thr415= Multiple submitters hypertriglyceridemia 2
- c.157-125del Single submitter
- c.576+12del Single submitter
- c.821+102G>A Single submitter
- c.822-8C>T Single submitter
- c.891-165_891-164insGAAT Single submitter
- c.*193C>A Single submitter
- p.Leu178= Single submitter
- p.Phe342= Single submitter
- p.Pro399= Single submitter
- p.Thr408= Single submitter
Benign/Likely benign 12
- c.28-9G>A Multiple submitters
- c.576+17C>G Multiple submitters
- p.Ala409Thr Multiple submitters
- p.Asp182Asn Multiple submitters hypertriglyceridemia 2
- p.Asp34= Multiple submitters
- p.Asp439= Multiple submitters
- p.Gly112Ser Multiple submitters
- p.Leu234Val Multiple submitters
- p.Ser173= Multiple submitters
- p.Ser449= Multiple submitters
- p.Ser90= Multiple submitters
- p.Thr347= Multiple submitters
Likely benign 96
- c.*5C>T Multiple submitters
- p.Ala257= Multiple submitters
- p.Ala409= Multiple submitters
- p.Leu172= Multiple submitters
- p.Pro235His Multiple submitters
- p.Ser85= Multiple submitters
- p.Ser95= Multiple submitters
- p.Thr108= Multiple submitters
- p.Thr415Met Multiple submitters
- p.Thr447= Multiple submitters
- c.1072+16C>T Single submitter
- c.1073-14C>T Single submitter
- c.1073-18C>T Single submitter
- c.1073-19G>A Single submitter
- c.157-18C>G Single submitter
- c.27+16T>A Single submitter
- c.27+17C>A Single submitter
- c.28-13C>T Single submitter
- c.28-18C>T Single submitter
- c.28-4C>G Single submitter
- c.28-7G>A Single submitter
- c.28-8C>T Single submitter
- c.576+20C>A Single submitter
- c.577-4G>C Single submitter
- c.577-5C>T Single submitter
- c.715-17C>T Single submitter
- c.821+11C>A Single submitter
- c.821+17C>T Single submitter
- c.822-11C>G Single submitter
- c.822-17C>T Single submitter
- c.890+14C>T Single submitter
- c.890+20G>T Single submitter
- c.976-15C>T Single submitter
- c.976-6C>T Single submitter
- c.976-7C>T Single submitter
- p.Ala163= Single submitter
- p.Ala325Thr Single submitter
- p.Ala354= Single submitter
- p.Ala373= Single submitter
- p.Ala442= Single submitter
- p.Ala457= Single submitter
- p.Arg249= Single submitter
- p.Arg261= Single submitter
- p.Arg385Gln Single submitter
- p.Arg392Gln Single submitter
- p.Asn177= Single submitter
- p.Asn57= Single submitter
- p.Asp459= Single submitter
- p.Asp51= Single submitter
- p.Asp61= Single submitter
- p.Asp86= Single submitter
- p.Asp96= Single submitter
- p.Gln258= Single submitter
- p.Gln98= Single submitter
- p.Glu380= Single submitter
- p.Glu387Lys Single submitter
- p.Gly129= Single submitter
- p.Gly159Val Single submitter
- p.Gly397= Single submitter
- p.His114Pro Single submitter
- p.His291= Single submitter
- p.Ile150Thr Single submitter ⚠
- p.Ile20= Single submitter
- p.Ile67= Single submitter
- p.Leu185= Single submitter
- p.Leu185del Single submitter
- p.Leu223= Single submitter
- p.Leu299= Single submitter
- p.Leu42= Single submitter
- p.Leu437= Single submitter
- p.Lys246Asn Single submitter
- p.Lys264= Single submitter
- p.Lys50= Single submitter
- p.Pro157= Single submitter
- p.Pro166= Single submitter
- p.Pro169= Single submitter
- p.Pro386= Single submitter
- p.Pro445= Single submitter
- p.Pro58= Single submitter
- p.Ser104= Single submitter
- p.Ser186= Single submitter
- p.Ser414= Single submitter
- p.Ser60Pro Single submitter
- p.Thr136= Single submitter
- p.Thr179= Single submitter
- p.Thr216= Single submitter
- p.Thr229= Single submitter
- p.Thr3= Single submitter
- p.Tyr239= Single submitter
- p.Val140= Single submitter
- p.Val143= Single submitter
- p.Val170= Single submitter
- p.Val311= Single submitter
- p.Val435= Single submitter
- c.821+3G>A No assertion criteria CREB3L3-related disorder
- p.Asn365= No assertion criteria CREB3L3-related disorder
Uncertain significance 151
- c.457+5G>A Multiple submitters hypertriglyceridemia 2
- p.Ala111Thr Multiple submitters ⚠
- p.Ala167Thr Multiple submitters ⚠
- p.Ala442Val Multiple submitters ⚠
- p.Arg248Cys Multiple submitters ⚠
- p.Arg32Gln Multiple submitters ⚠
- p.Arg357Gly Multiple submitters
- p.Cys210Arg Multiple submitters ⚠
- p.Glu387Gln Multiple submitters ⚠
- p.Gly105Glu Multiple submitters ⚠
- p.Gly121Glu Multiple submitters ⚠
- p.Gly159Glu Multiple submitters ⚠
- p.Gly321Asp Multiple submitters ⚠
- p.Gly43Cys Multiple submitters ⚠
- p.His196Tyr Multiple submitters ⚠
- p.Leu26Pro Multiple submitters ⚠
- p.Leu28Arg Multiple submitters ⚠
- p.Pro166Leu Multiple submitters ⚠
- p.Trp46Arg Multiple submitters
- p.Val180Met Multiple submitters
- c.1073-2A>G Single submitter
- c.1073-3_1073-2del Single submitter
- c.577-7T>A Single submitter
- c.715-3C>T Single submitter
- c.821+3G>C Single submitter
- c.822-3C>A Single submitter
- c.890+2dup Single submitter
- c.890+5G>A Single submitter
- c.891-7C>G Single submitter
- p.Ala11Val Single submitter ⚠
- p.Ala14Asp Single submitter ⚠
- p.Ala257Pro Single submitter ⚠
- p.Ala280Pro Single submitter ⚠
- p.Ala373Gly Single submitter ⚠
- p.Ala381Ser Single submitter ⚠
- p.Ala381Val Single submitter ⚠
- p.Ala428Thr Single submitter ⚠
- p.Ala436Thr Single submitter ⚠
- p.Ala452Glu Single submitter ⚠
- p.Ala456Val Single submitter ⚠
- p.Ala457Val Single submitter ⚠
- p.Arg103Cys Single submitter ⚠
- p.Arg103Leu Single submitter ⚠
- p.Arg175Pro Single submitter ⚠
- p.Arg204Gln Single submitter ⚠
- p.Arg242Pro Single submitter ⚠
- p.Arg248His Single submitter ⚠
- p.Arg252Gln Single submitter ⚠
- p.Arg274Gln Single submitter
- p.Arg274Trp Single submitter ⚠
- p.Arg357Gln Single submitter ⚠
- p.Arg357Ter Single submitter
- p.Arg370Cys Single submitter ⚠
- p.Arg370His Single submitter ⚠
- p.Arg385Gly Single submitter ⚠
- p.Arg385Ter Single submitter
- p.Arg426Lys Single submitter ⚠
- p.Arg451His Single submitter ⚠
- p.Asn2Asp Single submitter ⚠
- p.Asn345Lys Single submitter ⚠
- p.Asn413Lys Single submitter ⚠
- p.Asn420Ser Single submitter ⚠
- p.Asp171His Single submitter ⚠
- p.Asp191Glu Single submitter ⚠
- p.Asp21Asn Single submitter ⚠
- p.Asp31Gly Single submitter ⚠
- p.Asp34Gly Single submitter ⚠
- p.Asp374Val Single submitter ⚠
- p.Asp402Glu Single submitter ⚠
- p.Asp407Gly Single submitter ⚠
- p.Asp62Asn Single submitter ⚠
- p.Asp72Tyr Single submitter ⚠
- p.Asp96Asn Single submitter ⚠
- p.Cys162Tyr Single submitter hypertriglyceridemia 2 ⚠
- p.Cys176Phe Single submitter ⚠
- p.Cys210Ser Single submitter ⚠
- p.Gln312Arg Single submitter ⚠
- p.Gln52= Single submitter
- p.Glu219del Single submitter
- p.Glu259Gln Single submitter ⚠
- p.Glu293Lys Single submitter ⚠
- p.Glu301Lys Single submitter ⚠
- p.Glu348Lys Single submitter ⚠
- p.Glu380Asp Single submitter ⚠
- p.Glu44Gly Single submitter ⚠
- p.Glu455Gln Single submitter ⚠
- p.Glu460Lys Single submitter ⚠
- p.Gly198Arg Single submitter ⚠
- p.Gly35Ser Single submitter
- p.Gly378Arg Single submitter ⚠
- p.Gly404Ser Single submitter ⚠
- p.Gly431Val Single submitter ⚠
- p.Gly47Val Single submitter ⚠
- p.Gly84Asp Single submitter ⚠
- p.His114Arg Single submitter ⚠
- p.His114Leu Single submitter ⚠
- p.Ile20Asn Single submitter ⚠
- p.Ile247Phe Single submitter ⚠
- p.Ile247Val Single submitter ⚠
- p.Ile309Thr Single submitter ⚠
- p.Ile339Val Single submitter ⚠
- p.Leu124Phe Single submitter ⚠
- p.Leu152Pro Single submitter ⚠
- p.Leu183Pro Single submitter ⚠
- p.Leu215Phe Single submitter ⚠
- p.Leu303Val Single submitter ⚠
- p.Leu328Phe Single submitter
- p.Lys254Asn Single submitter ⚠
- p.Lys265del Single submitter
- p.Met17Val Single submitter ⚠
- p.Met275Arg Single submitter ⚠
- p.Phe342Leu Single submitter ⚠
- p.Phe359Leu Single submitter ⚠
- p.Pro115Ala Single submitter ⚠
- p.Pro115His Single submitter ⚠
- p.Pro118Ser Single submitter ⚠
- p.Pro118Thr Single submitter ⚠
- p.Pro144Leu Single submitter ⚠
- p.Pro19Ser Single submitter ⚠
- p.Pro377fs Single submitter
- p.Pro386Thr Single submitter ⚠
- p.Pro445Gln Single submitter ⚠
- p.Pro445Leu Single submitter ⚠
- p.Pro445Ser Single submitter ⚠
- p.Pro78Arg Single submitter ⚠
- p.Ser12Phe Single submitter ⚠
- p.Ser156Ile Single submitter ⚠
- p.Ser186Leu Single submitter ⚠
- p.Ser189Asn Single submitter ⚠
- p.Ser22Arg Single submitter ⚠
- p.Ser256Leu Single submitter ⚠
- p.Ser260Asn Single submitter ⚠
- p.Ser330Phe Single submitter ⚠
- p.Ser360Phe Single submitter ⚠
- p.Ser360Tyr Single submitter ⚠
- p.Ser369Tyr Single submitter ⚠
- p.Ser65Arg Single submitter ⚠
- p.Ser87Gly Single submitter
- p.Thr136Pro Single submitter ⚠
- p.Thr179Ala Single submitter
- p.Thr314Ala Single submitter ⚠
- p.Thr320Ile Single submitter
- p.Thr415fs Single submitter
- p.Trp155Gly Single submitter ⚠
- p.Trp403Ser Single submitter ⚠
- p.Trp80Gly Single submitter ⚠
- p.Val140Glu Single submitter ⚠
- p.Val289Leu Single submitter ⚠
- p.Val371Met Single submitter ⚠
- p.Val40Met Single submitter ⚠
- c.822-2A>G No assertion criteria CREB3L3-related disorder