Gene Validity Curation

ACTC1 - arrhythmogenic right ventricular cardiomyopathy

Gene: ACTC1 (HGNC:143)
Classification - 03/15/2019
Disease: arrhythmogenic right ventricular cardiomyopathy (MONDO_0016587)
Mode of Inheritance: Autosomal dominant inheritance (HP:0000006)
Replication over time: NO Contradictory Evidence: NO
Expert Panel: Arrythmogenic Right Ventricular Cardiomyopathy EP
Evidence Summary: ACTC1: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) HGNC: 143 MONDO_0016587 Mode of Inheritance: Autosomal dominant inheritance (HP:0000006) Expert Panel: Arrhythmogenic Right Ventricular Cardiomyopathy SOP: Gene Clinical Validity Standard Operating Procedures (SOP), Version 6 Calculated Classification (date) No reported evidence 22/02/2019 Evidence Summary: There is no evidence that ACTC1 is involved in ARVC. This gene has been investigated for pathogenic variants in three populations of patients meeting 2010 Task Force criteria for ARVC: a cohort of 14 Spanish unrelated patients (22421524), a cohort of 14 cases (27194543) and a cohort of 137 ARVC patients (29709087). No variants in ACTC1 were reported.
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
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5
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) 0
Experimental Evidence
Evidence Category Evidence Type Guidelines Points PMIDs/Notes
Default Range Max Count Total Counted
Function Biochemical Function 0.5 0 - 2 2
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2
Functional Alteration Patient cells 1 0 - 2 2
Non-patient cells 0.5 0 - 1
Models Non-human model organism 2 0 - 4 4
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
Total Experimental Evidence Points (Maximum 6) 0

 


 

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 0 0 0 NO
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)
No Known Disease Relationship
05/08/2020
EXPERT CURATION (DATE)
No Known Disease Relationship
03/15/2019
EVIDENCE SUMMARY
ACTC1: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) HGNC: 143 MONDO_0016587 Mode of Inheritance: Autosomal dominant inheritance (HP:0000006) Expert Panel: Arrhythmogenic Right Ventricular Cardiomyopathy SOP: Gene Clinical Validity Standard Operating Procedures (SOP), Version 6 Calculated Classification (date) No reported evidence 22/02/2019 Evidence Summary: There is no evidence that ACTC1 is involved in ARVC. This gene has been investigated for pathogenic variants in three populations of patients meeting 2010 Task Force criteria for ARVC: a cohort of 14 Spanish unrelated patients (22421524), a cohort of 14 cases (27194543) and a cohort of 137 ARVC patients (29709087). No variants in ACTC1 were reported.