ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function 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."

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.