ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.761C>T (p.Pro254Leu) (rs948484408)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000457579 SCV000553990 uncertain significance Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-10-05 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 254 of the SDHB protein (p.Pro254Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals with paraganglioma (PGL) (PMID: 17848412, 20208144, 19454582, 19351833). Currently there is insufficient evidence to conclude whether this variant segregates with disease or not (PMID: 17848412). ClinVar contains an entry for this variant (Variation ID: 412459). Structural analysis based on the crystal structure of SDHB suggests that this variant may lead to the conformational change that affects the binding of iron-sulfur (4Fe-4S) cluster (PMID: 17848412). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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