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Gene-Disease Validity Details

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Gene
Gene:
ANK2
HGNC:493
Disease:
Brugada syndrome
MONDO:0015263
Disputed
Classification - 11/21/2017
Mode of Inheritance:
Autosomal dominant inheritance
HP:0000006
SOP:
ClinGen Gene Validity Evaluation Criteria SOP5
 
Expert Panel:
Brugada Syndrome
 
 
Replication over time:
 
Contradictory Evidence:
NO
ClinGen Curation ID:
CCID:004126
    Additional evidence details have not been made available for this particular Gene-Disease assertion

ANK2 - Brugada syndrome

Modify Calculated Classification:
YES
Evidence Summary:
Genetic Evidence
Case-Level Data
 Evidence Type Case Information Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Variant Evidence
 Autosomal Dominant or X-linked Disorder Variant is de novo 2 0-3 12
Proband with predicted or proven null variant 1.5 0-2 10
Proband with other variant type with some evidence of gene impact 0.5 0-1.5 7
2.90
2.9
Mohler PJ et al. 2007 Jan 30 (PMID:17242276); Allegue C et al. 2015 (PMID:26230511); Ichikawa M et al. 2016 Nov 25 (PMID:27784853);
Autosomal Recessive Disease Two variants in trans and at least one de novo or a predicted/proven null variant 2 0-3 12
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5
Segregation Evidence Evidence of segregation in one or more families   Sequencing Method 0-3 3
 
Total LOD Score Candidate Gene Sequencing Exome/Genome or all genes sequenced in linkage region  
2-2.99 0.5 1
3-4.99 1 2
≥5 1.5 3
Case-Control Data
 Case-Control Study Type Case-Control Quality Criteria Guidelines Scores PMIDs/Notes
Points/Study Max Points Tally
Single Variant Analysis 1. Variant Detection Methodology
2. Power
3. Bias and confounding
4. Statistical Significance		 0-6 12
Aggregate Variant Analysis 0-6
Total Genetic Evidence Points (Maximum 12) 2.9
Experimental Evidence
 Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2
1
Protein Interaction 0.5 0 - 2 0.50
Mohler PJ et al. 2004 Dec 14 (PMID:15579534);
Expression 0.5 0 - 2 0.50
Mohler PJ et al. 2004 Dec 14 (PMID:15579534);
Functional Alteration Patient cells 1 0 - 2 2
Non-patient cells 0.5 0 - 1
Models Non-human model organism 2 0 - 4 4 1
Cell culture model 1 0 - 2
Rescue Rescue in human 2 0 - 4
Rescue in non-human model organism 2 0 - 4
1.00
Mohler PJ et al. 2007 Jan 30 (PMID:17242276);
Rescue in cell culture model 1 0 - 2
Rescue in patient cells 1 0 - 2
Total Experimental Evidence Points (Maximum 6) 2

 

 

Assertion criteria Genetic Evidence (0-12 points) Experimental Evidence
(0-6 points)		 Total Points
(0-18) 		Replication Over Time (Y/N)
Description Case-level, family segregation, or case-control data that support the gene-disease association Gene-level experimental evidence that support the gene-disease association Sum of Genetic & Experimental
Evidence 		> 2 pubs w/ convincing evidence over time (>3 yrs)
Assigned Points 2.9 2 4.9 NO
CALCULATED CLASSIFICATION LIMITED 1-6
MODERATE 7-11
STRONG 12-18
DEFINITIVE 12-18 AND replication over time
Valid contradictory evidence (Y/N)*
NO
CALCULATED CLASSIFICATION
LIMITED
MODIFY CALCULATED CLASSIFICATION
YES
CURATOR CLASSIFICATION
EXPERT CURATION (DATE)
DISPUTED
11/21/2017