ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

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Evidence for Loss Phenotypes

Evidence for loss of function 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,

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.