ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000003.11) (NC_000003.12)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

There is no evidence at present to show that MYL3 variants have a loss of function effect. MYL3 is associated with dominant hypertrophic cardiomyopathy. Described pathogenic missense variants in the MYL3 gene cause the disorder by altering its normal physiologic function (e.g: impairing essential interaction with other components of the sarcomere) (PMID: 22131351 ). There is one report of a case with recessive inheritance due to autozygosity. The variant reported in recessive HCM was a homozygous missense change (p.Glu143Lys). Functional studies were not performed (PMID: 12021217, 21823217). ClinVar classifies the Glu143Lys variant as "uncertain" and reports it found in individuals with pathogenic changes in other genes. One report describes a splice site alteration predicted to cause exon skipping and no parental studies were done (PMID: 19035361). One frameshift variant in the middle of the gene has been described but it is unclear if it was causative of HCM or not (PMID: 25132132), and there are two instances of frameshift and one of an early canonical splice site change in ExAc (all at very low freq). There are three transcripts for MYL3 with different reading frames at the frameshift locations. The Database of Genomic Variants (DGV) lists a number of deletion CNVs including MYL3 and reported by multiple groups.

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

Triplosensitivity phenotype comment:

There is no evidence for triplosensitivity of MYL3 at present.