Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

KIF1B : Hereditary pheochromocytoma-paraganglioma

HGNC:16636 | OrphaNet: 29072 | OMIM:605995
Mode of Inheritance: Autosomal dominant inheritance (HP:0000006)
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 4.0 4
Welander J et al. 2014 Jul (PMID:24694336); Yeh IT et al. 2008 Oct (PMID:18726616); Schlisio S et al. 2008 Apr 1 (PMID:18334619);
Proband with other variant type with some evidence of gene impact 0.5 0-1.5 7 0.0 0
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 LOD Score Examples 3 5 0-7 7
2 4
1.5 3
1 1.5
   
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 12
Total Genetic Evidence Points (Maximum 12) 4
Experimental Evidence
 Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2 2.0 2
Chen ZX et al. 2014 Apr (PMID:24469107); Schlisio S et al. 2008 Apr 1 (PMID:18334619); Welander J et al. 2012 Dec 15 (PMID:23010473);
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2
Functional Alteration Patient cells 1 0 - 2 2 0.0 0
Non-patient cells 0.5 0 - 1
Models & Rescue Animal model 2 0 - 4 4 0.0 0
Cell culture model system 1 0 - 2
Rescue in animal model 2 0 - 4
Rescue in engineered equivalent 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 4 2 6 YES
CALCULATED CLASSIFICATION LIMITED 1-6
MODERATE 7-11
STRONG 12-18
DEFINITIVE 12-18 AND replication over time
Valid contradictory evidence (Y/N)*
CALCULATED CLASSIFICATION (DATE)
LIMITED
06/22/2017
EXPERT CURATION (DATE)
LIMITED
06/22/2017
Assertion made by the Hereditary Cancer Working Group.