ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000017.10) (NC_000017.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
25003005 Tuzovic et al (2013) identified a de novo heterozygous nonsense MYH10 variant (p.E908X) in a patient with severe intellectual disability, microcephaly and multiple congenital anomalies including congenital diaphragmatic hernia. Iglesias et at (2014) also described the same patient in their whole-genome sequencing report (PMID: 24901346). The myosin heavy chain 10 (MYH10) gene encodes for non-muscle myosin IIB (NM IIB). Tuzovic et al generated a mouse model with a hypomorphic, homozygous R709C missense mutation in the motor domain of NM IIB. In this study, the homozygous mutants show 73% reduction in the expression of the NMHC-IIB and died in the early postnatal period. Brain tissue obtained from homozygous mutant mice show distorted cerebral cortex due to hydrocephalus and small and underdeveloped cerebellum. Those that survived longer showed severe growth retardation and progressive hydrocephalus and ataxia. Heterozygous mutants survived to adulthood without any obvious abnormalities. Further studies on germline ablated NMHC IIB mice and R709C mutant mice showed that both developed progressive hydrocephalus starting from E11.5, although the R709C mice develop it at a slower rate.
25284784 Dong et al (2014) described a de novo frameshift MYH10 variant in a patient with intellectual disability and autism spectrum disorder.
25363768 Iossifov et al (2014) identified de novo one frameshift and two missense variants in MYH10 in patients with autism spectrum disorder.

Haploinsufficiency phenotype comments:

Several missense, nonsense, and frameshift variants have been identified in myosin heavy chain 10 (MYH10) in patients with neurodevelopmental disorders, including autism spectrum disorder and intellectual disability (PMIDs: 25003005; 25363768; 25356899; 24901346; 25284784; 24901346; 25849321). However, there are currently no reported partial or entire deletions of MYH10. In humans, myosin heavy chain 10 (MYH10) encodes for the heavy chain of non-muscle myosin IIB (NM IIB). NM IIB is enriched in neuronal tissue during mouse embryonic development and is critical for neuronal cell migration in cerebral cortex, cerebellum and pontine and facial neurons (PMIDs: 15034141; 16481398). NM IIB also plays a critical role in mouse cardiac development and is expressed in the cardiac myocytes during embryonic development (PMID: 9356462). Further, germline homozygous loss of function mutations in NM IIB are embryonically lethal in mice and are associated with severe progressive hydrocephalus (PMID: 11283949).

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

Triplosensitivity phenotype comment:

There have been no reports of entire duplications of MYH10. At this time there is no evidence that supports the triplosensitivity of this gene.