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
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.
Ambry Genetics	RCV000562737	SCV000675118	uncertain significance	Hereditary cancer-predisposing syndrome	2019-04-18	criteria provided, single submitter	clinical testing	Insufficient or conflicting evidence
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759346	SCV000888624	uncertain significance	not provided	2018-07-09	criteria provided, single submitter	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148873	SCV000190617	uncertain significance	Pheochromocytoma	2014-06-01	no assertion criteria provided	research

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