ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.158C>T (p.Pro53Leu) (rs149516118)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562737 SCV000675118 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
CSER_CC_NCGL; University of Washington Medical Center RCV000148873 SCV000190617 uncertain significance Pheochromocytoma 2014-06-01 no assertion criteria provided research
Invitae RCV000560900 SCV000640146 uncertain significance Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2018-08-26 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 53 of the SDHD protein (p.Pro53Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs149516118, ExAC 0.01%). This variant has been reported to segregate with hereditary paraganglioma pheochromocytoma syndrome in a single family (PMID: 25819804). However, in this same family, it is highly likely that this variant occurred on the same chromosome as a pathogenic truncation in the SDHD gene in all affected family members, which suggests the c.158C>T change may not be the primary cause of disease in this family. This variant has also been reported in an individual affected with sporadic pheochromocytoma (PMID: 22517554). ClinVar contains an entry for this variant (Variation ID: 161388). Experimental studies in yeast have shown that this missense change does not disrupt protein function (PMID: 23175444). In summary, this variant has been shown not to disrupt SDHD function in yeast. It has been reported in both the population and in affected individuals. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759346 SCV000888624 uncertain significance not provided 2018-07-09 criteria provided, single submitter clinical testing

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