Gene Validity Classification Summary

Gene/Disease Pair:

SLC22A5 : systemic primary carnitine deficiency disease

HGNC:10969 | MONDO_0008919
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 8
12.25
12
Nezu J et al. 1999 Jan (PMID:9916797); Tang NL et al. 1999 Apr (PMID:10072434); Wang Y et al. 1999 Mar 2 (PMID:10051646); Burwinkel B et al. 1999 Aug 2 (PMID:10425211); Vaz FM et al. 1999 Jul-Aug (PMID:10480371);
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5 3
2.5
Vaz FM et al. 1999 Jul-Aug (PMID:10480371); Wang Y et al. 2000 (PMID:10679939);
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) 12
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
1.5
Tamai I et al. 1998 Aug 7 (PMID:9685390);
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2 2 1
Wang Y et al. 1999 Mar 2 (PMID:10051646); Tamai I et al. 1998 Aug 7 (PMID:9685390);
Functional Alteration Patient cells 1 0 - 2 2 1
1
2
Rasmussen J et al. 2014 May 22 (PMID:27896095);
Non-patient cells 0.5 0 - 1 2 1
Tang NL et al. 1999 Apr (PMID:10072434); Wang Y et al. 2000 (PMID:10679939);
Models Non-human model organism 2 0 - 4 4 1 2 3
Lu Km et al. 1998 Nov 27 (PMID:9837751);
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
Vaz FM et al. 1999 Jul-Aug (PMID:10480371);
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
10/11/2018
EXPERT CURATION (DATE)
Definitive
04/24/2018