ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

  • 12q24.11
  • GRCh37/hg19 chr12: 111,348,623-111,358,404
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr12: 110,910,845-110,920,579
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000012.11) (NC_000012.12)

Haploinsufficiency phenotype comments:

MYL2 is associated with cardiomyopathy by different pathogenic mechanisms with different modes of inheritance that can be recessive or dominant, depending on genotype. Homozygous or compound heterozygous loss-of -function variants have been reported to cause autosomal recessive form cardiomyopathy. Furthermore, the heterozygous carriers did not show evidence of the disorder (PMID: 24111713, 23365102). Other missense changes cause autosomal dominant hypertrophic cardiomyopathy presumably due to loss of the normal physiologic function, for instance, loss of the contraction power stoke or altered actin sliding velocities (PMID: 25825243; 25324513). One paper describes a founder missense pathogenic variant capable of causing HCM by itself or augmented by other factor such as arterial hypertension (PMID: 26497160). MYL2 variants, among others, identified as incidental findings in an exome cohort (PMID: 23861362). There are several heterozygous frameshifts, stop gains, and splice site disruptions listed in ExAc for MYL2 implying that haploinsufficiency is not a disease mechanism for this gene.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No evidence at present for triplosensitivity of MYL2.