ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000019.9) (NC_000019.10)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
28263302 C Yuen RK et. al., 2017. Reported WGS of 5,205 samples from families with ASD, accompanied by clinical information, in an effort to build a resource, named MSSNG, to enable the sub-categorization of phenotypes and underlying genetic factors involved. Among all patients with de novo LOF variants, a patient (ID: 1-0590-003) was found to carrier a de novo frame shift 1-bp deletion in LMTK3 gene (supplementary table 4). No functional study was performed.
22542183 Iossifov et al. 2012. Exome sequencing of a subset of the Simons Simplex Collection including 343 families, each with a single child on the autism spectrum and at least one unaffected sibling. This study revealed de novo small indels and point substitutions came mostly from the paternal line in a age-dependent manner. Although there was no significant different numbers of de novo missense mutations in affected versus unaffected children, gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent in the affected group. Among them, a de novo frame shift variant was identified in a Proband (patient 13092). But no functional study was performed neither. Of note,

Haploinsufficiency phenotype comments:

PMID: 28008999. A GWAS study in Poland aimed to define the genetic architecture of pediatric and adult-onset inflammatory bowel diseases (IBDs for the Polish population. This study recruited a total of 1495 patients, including 761 patients with Crohn?s disease (424 pediatric), 734 patients with ulcerative colitis (390 pediatric), and 934 healthy controls. multiple pediatric patients were found to be homozygous for a missense variant (p.Glu1315Asp) in LMTK3 gene, while it is not present in adults or healthy controls as homozygotes. No functional study was performed.

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