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
19546167 Bayley et al (2009) describe patients with multi-exon deletions with paraganglioma, including one individual with a deletion of exons 5 and 6 of the SDHC.
15342702 Baysal et al. (2004) described a multiplex "family with head and neck paragangliomas 8.37 kb SDHC deletion, which spans two AluY elements and removes exon 6." They identified the same deletion in a reportedly unrelated sporadic case; further investigation identified "allele sharing with the familial cases at seven polymorphic markers near SDHC, suggesting a common ancestral origin."
17667967 Pasini et al. (2008) described germline SDHC variants in individuals with paraganglioma and gastrointestinal stromal tumors. The authors identified one novel nonsense variant (c.43C>T; p. Arg15X) and one splice-site substitution (IVS5+1G>A or c.405+1G>A), which resulted in "exon 5 [being] spliced out, causing a frameshift and a stop codon in the 3? untranslated region of the gene."

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.