ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.600G>T (p.Trp200Cys) (rs397516836)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162460 SCV000212817 pathogenic Hereditary cancer-predisposing syndrome 2018-02-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),Structural Evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000462889 SCV000554005 pathogenic Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-07-29 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with cysteine at codon 200 of the SDHB protein (p.Trp200Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals and families affected with paragangliomas (PMID: 17200167, 17143317, 18382370, 19184535, 19802898, 20119652) or gastrointestinal stromal tumors (PMID: 21173220). A number of these cases were reported as malignant or metastatic (PMID: 17200167, 19184535, 20119652). ClinVar contains an entry for this variant (Variation ID: 183747). Experimental studies have shown that this missense change results in reduced protein stability (PMID: 22835832). For these reasons, this variant has been classified as Pathogenic.
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000505334 SCV000599516 pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research

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