ClinGen Dosage Sensitivity Curation Page

TIGD6

  • Curation Status: Complete

Location Information

Select assembly: (NC_000005.9) (NC_000005.10)
  • Haploinsufficiency score: Haploinsufficiency unlikely
  • Strength of Evidence (disclaimer): Haploinsufficiency unlikely
Evidence for haploinsufficiency phenotype
PubMed ID Description
32487729 Rausell et al. (2020) suggested that this gene is dosage sensitivity unlikely because it had at least one homozygous LoF variant present in >1% of the gnomAD population. Examples of homozygous likely LoF variants in this gene in gnomAD include p.Pro379TyrfsTer7 (1 homozygous individual), p.Glu345LysfsTer11 (51722 homozygous individuals), and p.Gly6AspfsTer7 (1085 homozygous individuals).
22344438 MacArthur et al. (2012) suggested that this gene is dosage sensitivity unlikely because it had at least one homozygous LoF variant present at >5% of the 1000 Genomes Project database.
25807282 Sulem et al. (2015) identified 5927 individuals in an Icelandic population with a homozygous LoF variants in this gene. This population was participating in a variety of disease projects and the researchers pulled this population to investigate how often homozygous LoF variants were found in this population.
28406212 Saleheen et al. (2017) identified 2 adult individuals in a Pakistani population with a homozygous LoF variants in this gene. The individuals were originally recruited for a study evaluating risk of myocardial infarction. Individuals within that study found to have homozygous predicted LOF variants were phenotyped for ?more than 200 biochemical and disease traits?.
26940866 Narasimhan et al. (2016) identified rare homozygous loss-of-function (rnLOF) variants in a British Pakistani population characterized as healthy, pregnant, or type 2 diabetic. The variants were compared with an Icelandic population and the ExAC database and a TIGD6 variant was found in the British Pakistani and ExAC populations.
32461654

Haploinsufficiency phenotype comments:

This gene was classified as dosage sensitivity unlikely on 2/3/2021 based on review of population data as described in the PMIDs above. These genes all have at least one curated homozygous loss of function variant in 1% or greater of the gnomAD population dataset and some have also been observed in additional population datasets. As of January 2021, there are no disease associations found in OMIM, and no reports suggesting a Mendelian disease association in the literature. The gnomAD pLI score is 0 and the LOEUF score is 1.21 predicting that this gene is tolerant of LoF variation.

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