Catecholaminergic Polymorphic Ventricular Tachycardia

Gene: CALM3

I don't know

Not assessed by ClinGen as at 03.05.2020.
Red in PanelApp GEL

Pathogenic and likely pathogenic CALM 1, 2 and 3 variants have been asscoiated with CPVT, LQTS and Idopathic VF (including sudden unexplained death) in a review paper formt he CALM registry (PMID: 31170290). For CPVT at least:
- 7 families have been reported with one of 2 CALM1 P/LP variants, both variants caused overlapping phenotype of LQTS, CPVT and/or SUD
- 8 families have been reported with one of 4 CALM2 P/LP variants, 3 of which caused overlapping phenotype of LQTS, CPVT and/or SUD
- 2 families have been reported with one of 2 CALM3 P/LP variants, both of which caused CPVT exclusively.

Calmodulin is an essential calcium-sensing, signal-transducing protein. Three calmodulin genes, CALM1, CALM2 and CALM3, have unique nucleotide sequences but encode identical 149-amino acid calmodulin proteins with 4 EF-hand calcium-binding loops. (OMIM: https://omim.org/entry/114180?search=CALM1&highlight=calm1#7, accessed 03.05.2020)

Created: 3 Jun 2020, 2:30 a.m. | Last Modified: 3 Jun 2020, 2:30 a.m.

Panel Version: 0.10

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
LQTS; idiopathic VF, sudden unexplained death

Publications

• PMID: 31170290

Red List (low evidence)

Single family reported with CPVT.

Created: 6 Mar 2020, 8:02 a.m. | Last Modified: 6 Mar 2020, 8:02 a.m.

Panel Version: 0.9

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ventricular tachycardia, catecholaminergic polymorphic 6 618782

Publications

• 27516456

Green List (high evidence)

PMID: 31454269; 4 families including 1 consanguineous family with LQTS. Functional studies indicate reduced calcium binding for Glu141Lys and Glu141Val

Created: 6 Mar 2020, 3:35 a.m. | Last Modified: 6 Mar 2020, 3:40 a.m.

Panel Version: 0.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Long QT syndrome 16 (MIM# 618782)

Publications

• PMID: 31454269