Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

ECHS1 : mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency

HGNC:3151 | MONDO_0014563
Mode of Inheritance: Autosomal recessive inheritance (HP:0000007)
Expert Panel: Fatty Acid Oxidation Disorders EP
SOP: Gene Clinical Validity Standard Operating Procedures (SOP), Version 6

Genetic Evidence
Case-Level Data
Evidence Type Case Information Type Guidelines Points PMIDs/Notes
Default Range Max Count Total Counted
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
Autosomal Recessive Disease Two variants in trans and at least one de novo or a predicted/proven null variant 2 0-3 12 2
4
11.75
Haack TB et al. 2015 May (PMID:26000322); Al Mutairi F et al. 2017 Apr (PMID:27905109);
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5 13
7.75
Peters H et al. 2014 Nov (PMID:25125611); Sakai C et al. 2015 Feb (PMID:25393721); Yamada K et al. 2015 Oct (PMID:26251176); Haack TB et al. 2015 May (PMID:26000322); Ferdinandusse S et al. 2015 Jun 18 (PMID:26081110);
Segregation Evidence   Summed LOD Family Count  
Candidate gene sequencing
Exome/genome or all genes sequenced in linkage region
Total Summed LOD Score    
Case-Control Data
Case-Control Study Type Case-Control Quality Criteria Guidelines Points PMIDs/Notes
Points/Study Max Count Points Counted
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) 11.75
Experimental Evidence
Evidence Category Evidence Type Guidelines Points PMIDs/Notes
Default Range Max Count Total Counted
Function Biochemical Function 0.5 0 - 2 2 1
0.5
1
Peters H et al. 2014 Nov (PMID:25125611);
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2 1 0.5
Kanazawa M et al. 1993 (PMID:8012501);
Functional Alteration Patient cells 1 0 - 2 2
Non-patient cells 0.5 0 - 1
Models Non-human model organism 2 0 - 4 4 1
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 1 1
Sakai C et al. 2015 Feb (PMID:25393721);
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 11.75 2 13.75 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
10/15/2018
EXPERT CURATION (DATE)
Definitive
10/09/2018