ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.647A>G (p.Tyr216Cys) (rs1553177291)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000572107 SCV000664558 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
Invitae RCV000633963 SCV000755236 uncertain significance Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-03-02 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 216 of the SDHB protein (p.Tyr216Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with paraganglioma (PMID: 26096992). ClinVar contains an entry for this variant (Variation ID: 480804). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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