Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

KCNT1 : Childhood-Onset Epilepsy Syndrome

MONDO:0020072 | ORPHA:293181 | OMIM:608167
Mode of Inheritance: Other
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
18.00
12
Barcia G et al. 2012 Nov (PMID:23086397); De Sanctis V et al. 2013 Sep (PMID:24079078); Fagerberg L et al. 2014 Feb (PMID:24309898); Rizzo F et al. 2016 Apr (PMID:26784557);
Proband with predicted or proven null variant 1.5 0-2 10 0.00 0
Proband with other variant type with some evidence of gene impact 0.5 0-1.5 7
0.00
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
 
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) 12
Experimental Evidence
Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2
1.00
1
Yuan A et al. 2003 Mar 6 (PMID:12628167);
Protein Interaction 0.5 0 - 2 0.00
Rizzi S et al. 2016 Jul 1 (PMID:26587966);
Expression 0.5 0 - 2 0.00
Wallén P et al. 2007 Nov 15 (PMID:17884929); Vuorinen T et al. 1989 Aug (PMID:2548562); Martin HC et al. 2014 Jun 15 (PMID:24463883); Tang QY et al. 2016 Jan 5 (PMID:26725113); Barcia G et al. 2012 Nov (PMID:23086397); Joiner WJ et al. 1998 Oct (PMID:10196543); Milligan CJ et al. 2014 Apr (PMID:24591078);
Functional Alteration Patient cells 1 0 - 2 2
0.00
1
Non-patient cells 0.5 0 - 1 1.00
Barcia G et al. 2012 Nov (PMID:23086397); Milligan CJ et al. 2014 Apr (PMID:24591078); Tang QY et al. 2016 Jan 5 (PMID:26725113);
Models Non-human model organism 2 0 - 4 4 0.00 0
Joiner WJ et al. 1998 Oct (PMID:10196543);
Cell culture model 1 0 - 2 0.00
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
Mikati MA et al. 2015 Dec (PMID:26369628); Milligan CJ et al. 2014 Apr (PMID:24591078);
Rescue in patient cells 1 0 - 2 0.00
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 12 2 14 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
09/05/2017
EXPERT CURATION (DATE)
DEFINITIVE
10/20/2017