ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

  • 11q23.1
  • GRCh37/hg19 chr11: 111,957,548-111,966,525
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr11: 112,086,873-112,095,794
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000011.9) (NC_000011.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
10657297 Baysal et al. 2000 describe SDHD variants in five families with hereditary paraganglioma, including two nonsense variants. The authors report that " none of the mutations has been observed in more than 200 normal control chromosomes...[and that] the mutations cosegregate with the disease phenotype in all affected individuals. "
12111639 Cascon et al. (2002) report variants in SDHD identified in individuals with paraganglioma and/or pheochromocytoma, including one nonsense variant and one "4-bp frameshift deletion in codon 112 (13732delGACT)" that reportedly "gave rise to a 132-amino acid-truncated protein by creating a premature stop codon."

Haploinsufficiency phenotype comments:

Several deletions involving SDHD have also been reported, though many of these often include adjacent genes (either in part or in their entirety). For example, McWhinney (2004) et al describe one family with a 96 kb deletion including the entire SDHD gene with a history of paraganglioma (PMID:15531530) . The authors note that this region may also include part of the adjacent TIMM8B gene. Bayley et al (2009) describe two patients with paraganglioma who are deleted for exons 1 and 2 of SDHD as well as the promoter. These deletions also included varying amounts of TIMM8B and other genes (PMID:19546167). Additionally, Caninanos et al (2011) describe one family with paraganglioma and a 25 kb deletion involving the promotor and exons 1 and 2 of SDHD, as well as 5 other genes (DLAT, PIH1D2, C11orf57, TIMM8B, SDHD) (PMID: 20310044).

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