CALM2
Chr 2ADcalmodulin 2
Also known as: CALM, CALML2, CAM1, CAM3, CAMC, CAMII, CAMIII, LQT15
Calmodulin mediates calcium signal transduction by binding calcium and regulating numerous enzymes, ion channels, and proteins throughout the cell. Mutations cause Long QT syndrome 15, which can present in infancy with life-threatening ventricular arrhythmias, delayed neurodevelopment, and epilepsy, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, reflecting its essential cellular role.
Primary Disease Associations & Inheritance
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
260 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 10 | 12 | 0 | 22 |
Likely Pathogenic | 0 | 9 | 2 | 0 | 11 |
VUS | 2 | 48 | 22 | 5 | 77 |
Likely Benign | 0 | 5 | 83 | 35 | 123 |
Benign | 0 | 0 | 14 | 0 | 14 |
Conflicting | — | 5 | |||
| Total | 2 | 72 | 133 | 40 | 252 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CALM2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools