Gene Validity Classification Summary

Gene/Disease Pair:

SCN3B : Brugada Syndrome

MONDO:0011001 | ORPHA:130 | OMIM:601144
Mode of Inheritance: Autosomal dominant inheritance (HP:0000006)
SOP: Gene Clinical Validity Standard Operating Procedures (SOP), Version 5

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
0.50
0.5
Hu D et al. 2009 Jun (PMID:20031595); Ishikawa T et al. 2013 (PMID:23257389); Peeters U et al. 2015 (PMID:26179811); Liu C et al. 2014 Mar (PMID:24529773); Tan BH et al. 2010 Jun (PMID:20226894);
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 Canditate 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) 0.5
Experimental Evidence
Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2
0.50
1
Fahmi AI et al. 2001 Dec 15 (PMID:11744748); Ko SH et al. 2005 Jan (PMID:15455233); Maier SK et al. 2004 Mar 23 (PMID:15007009);
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2 0.50
Hu D et al. 2009 Jun (PMID:20031595); Olesen MS et al. 2011 Mar 1 (PMID:21051419); Hakim P et al. 2008 Oct-Nov (PMID:19351516);
Functional Alteration Patient cells 1 0 - 2 2
Non-patient cells 0.5 0 - 1
Hu D et al. 2009 Jun (PMID:20031595); Ishikawa T et al. 2013 (PMID:23257389);
Models Non-human model organism 2 0 - 4 4 2.00 2
Hakim P et al. 2008 Oct-Nov (PMID:19351516); Okata S et al. 2016 Sep 28 (PMID:27677334);
Cell culture model 1 0 - 2
Rescue Rescue in human 2 0 - 4
Rescue in non-human model organism 2 0 - 4
Rescue in cell culture model 1 0 - 2
Rescue in patient cells 1 0 - 2
Total Experimental Evidence Points (Maximum 6) 3

 


 

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 0.5 3 3.5 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 (DATE)
LIMITED
12/01/2016
MODIFY CALCULATED CLASSIFICATION
YES
CURATOR CLASSIFICATION (DATE)
EXPERT CURATION (DATE)
DISPUTED
11/21/2017