Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

SCN5A : 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 3.00 3
Vatta M et al. 2002 Apr (PMID:12051963); Chen Q et al. 1998 Mar 19 (PMID:9521325);
Proband with other variant type with some evidence of gene impact 0.5 0-1.5 7
2.50
2.5
Vatta M et al. 2002 Apr (PMID:12051963); Deschênes I et al. 2000 Apr (PMID:10727653); Chen Q et al. 1998 Mar 19 (PMID:9521325); Bezzina C et al. 1999 Dec 3-17 (PMID:10590249);
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
3.00
3  
Total LOD Score Canditate Gene Sequencing Exome/Genome or all genes sequenced in linkage region  
2-2.99 0.5 1
Chen Q et al. 1998 Mar 19 (PMID:9521325);
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
5.50
Kapplinger JD et al. 2010 Jan (PMID:20129283); Schulze-Bahr E et al. 2003 Jun (PMID:14961552);
Total Genetic Evidence Points (Maximum 12) 12
Experimental Evidence
 Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2
Functional Alteration Patient cells 1 0 - 2 2
Liang P et al. 2016 Nov 8 (PMID:27810048);
Non-patient cells 0.5 0 - 1
Rook MB et al. 1999 Dec (PMID:10690282);
Models Non-human model organism 2 0 - 4 4 1
Cell culture model 1 0 - 2 1.00
Liang P et al. 2016 Nov 8 (PMID:27810048);
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) 1

 

 

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 12 1 13 YES
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)
DEFINITIVE
07/13/2017
EXPERT CURATION (DATE)
DEFINITIVE
11/21/2017