Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

SCN8A : Infantile Epilepsy Syndrome

MONDO:0020071 | ORPHA:442835 | OMIM:614558
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
34.50
12
Larsen J et al. 2015 Feb 3 (PMID:25568300);
Proband with predicted or proven null variant 1.5 0-2 10 0.00 0
Carvill GL et al. 2013 Jul (PMID:23708187); Estacion M et al. 2014 Sep (PMID:24874546); Vaher U et al. 2014 Dec (PMID:24352161);
Proband with other variant type with some evidence of gene impact 0.5 0-1.5 7
0.25
0.25
Autosomal Recessive Disease Two variants in trans and at least one de novo or a predicted/proven null variant 2 0-3 12
0.00
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5
0.00
Segregation Evidence Evidence of segregation in one or more families   Sequencing Method 0-3 3
0.00
0  
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
0.00
Aggregate Variant Analysis 0-6
0.00
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
0.00
2
Veeramah KR et al. 2012 Mar 9 (PMID:22365152); Burgess DL et al. 1995 Aug (PMID:7670495); Wagnon JL et al. 2015 Jan 15 (PMID:25227913); O et al. 2013 Oct 28 (PMID:24194747);
Protein Interaction 0.5 0 - 2 0.50
Wagnon JL et al. 2015 Jan 15 (PMID:25227913);
Expression 0.5 0 - 2 2.00
Functional Alteration Patient cells 1 0 - 2 2
1.00
1
Non-patient cells 0.5 0 - 1 0.00
Models Non-human model organism 2 0 - 4 4 4.00 4
Cell culture model 1 0 - 2 0.00
Veeramah KR et al. 2012 Mar 9 (PMID:22365152);
Rescue Rescue in human 2 0 - 4
0.00
Rescue in non-human model organism 2 0 - 4
0.00
Rescue in cell culture model 1 0 - 2 0.00
Rescue in patient cells 1 0 - 2 0.00
Total Experimental Evidence Points (Maximum 6) 6

 


 

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 6 18 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
07/18/2017
EXPERT CURATION (DATE)
DEFINITIVE
10/20/2017