ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.331G>A (p.Val111Ile) (rs201869798)

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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 RCV000565076 SCV000675110 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000457464 SCV000554067 uncertain significance Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2018-09-12 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 111 of the SDHD protein (p.Val111Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs201869798, ExAC 0.02%). This variant has been reported in an individual affected with pheochromocytoma (PMID: 17308434). ClinVar contains an entry for this variant (Variation ID: 412515) Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and an affected individual, but 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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