Myofibrillar Myopathy

Actionability Adult Summary Report

Genes: DES (HGNC:2770) BAG3 (HGNC:939) FLNC (HGNC:3756)
Mode(s) of Inheritance:Autosomal Dominant
Literature Search: 05/18/2026
Curation Status: Retracted (3.0.0)
Release History
Related Reports
Pediatric Summary Report

Secondary Findings in Adult Subjects. Non-diagnostic, excludes newborn screening & prenatal testing/screening.

The Actionability Summary Report is not available for this topic because there was insufficient evidence for actionability in the early rule out stage.

Actionability Assertions

Gene Condition (MONDO ID) OMIM ID Final Assertion
DES myofibrillar myopathy 1 (0011076) 601419 Moderate Actionability
BAG3 myofibrillar myopathy 6 (0013061) 612954 N/A - Insufficient evidence: expert review
FLNC myofibrillar myopathy 5 (0012289) 609524 Moderate Actionability

Actionability Assertion Rationale

  • The preliminary assertion for DES based on the rubric was strong. However, due to a lack of studies specific to myofibrillar myopathy to clearly inform effectiveness, the experts changed the assertion to moderate. The preliminary assertion for FLNC based on the rubric was moderate, and the experts agreed. There was significant discussion regarding potentially higher actionability with the dilated cardiomyopathy phenotype, which has yet to be assessed for DES and FLNC.

Actionability Scores

Outcome / Intervention Pair Severity Likelihood Effectiveness Nature of Intervention Total Score
Clinically significant cardiac involvement (DES) / Cardiology management 2 3A 2D 3 10AD
Clinically significant cardiac involvement (DES) / ICD implantation 2 3A 2C 2 9AC
Clinically significant cardiac involvement (FLNC) / Cardiology management 2 2A 2D 3 9AD
Clinically significant cardiac involvement (FLNC) / ICD implantation 2 2A 2D 2 8AD
View scoring key
Domain of Actionability Scoring Metric State of the Knowledgebase
Severity: What is the nature of the threat to health to an individual? 3 = Sudden death as a reasonably possible outcome
2 = Reasonable possibility of death or major morbidity
1 = Modest morbidity
0 = Minimal or no morbidity 		N/A
Likelihood: What is the chance that the outcome will occur? 3 = >40% chance
2 = 5%-39% chance
1 = 1%-4% chance
0 = <1% chance 		A = Substantial evidence or evidence from a high tier (tier 1)
B = Moderate evidence or evidence from a moderate tier (tier 2)
C = Minimal evidence or evidence from a lower tier (tier 3 or 4)
D = Poor evidence or evidence not provided in the report
N = Evidence based on expert contributions (tier 5)
Effectiveness: What is the effectiveness of a specific intervention in preventing or diminishing the risk of harm? 3 = Highly effective
2 = Moderately effective
1 = Minimally effective
0 = Controversial or unknown effectiveness
IN = Ineffective/No interventiona 		A = Substantial evidence or evidence from a high tier (tier 1)
B = Moderate evidence or evidence from a moderate tier (tier 2)
C = Minimal evidence or evidence from a lower tier (tier 3 or 4)
D = Poor evidence or evidence not provided in the report
N = Evidence based on expert contributions (tier 5)
Nature of intervention: How risky, medically burdensome, or intensive is the intervention? 3 = Low risk, or medically acceptable and low intensity
2 = Moderate risk, moderately acceptable or intensive
1 = Greater risk, less acceptable and substantial intensity
0 = High risk, poorly acceptable or intensive 		N/A
a Do not score the remaining categories

Early Rule-Out Summary

This topic did not pass the early rule out stage when reviewed on 06/24/2026 due to insufficient evidence for actionability. Thus, this topic did not move forward for a full evidence curation and summary report. This topic may be reconsidered if additional evidence becomes available.

Findings of Early Rule-Out Assessment

  1. Is there a qualifying resource, such as a practice guideline or systematic review, for the genetic condition?
  2. Does the practice guideline or systematic review indicate that the result is actionable in one or more of the following ways?

    3. a. Patient Management

    b. Surveillance or Screening

    c. Circumstances to Avoid

  3. Is it actionable in an undiagnosed adult with the condition?
  4. Is this condition an important health problem?
  5. Is there at least on known pathogenic variant with at least moderate penetrance (≥40%) or moderate relative risk (≥2) in any population?