ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.641A>G (p.Gln214Arg) (rs781590955)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469213 SCV000554040 uncertain significance Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2016-10-06 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 214 of the SDHB protein (p.Gln214Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with either pheochromocytoma or paraganglioma (PMID: 24659481). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on splicing and protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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