ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.209G>A (p.Arg70Lys) (rs755047928)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230516 SCV000287816 uncertain significance Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2018-08-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with lysine at codon 70 of the SDHD protein (p.Arg70Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is present in population databases (rs755047928, ExAC 0.001%). This variant has not been reported in the literature in individuals with SDHD-related disease. ClinVar contains an entry for this variant (Variation ID: 239463). 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. The observation of one or more missense substitutions at this codon (p.Arg70Thr, p.Arg70Met, p.Arg70Ser, and p.Arg70Gly) in affected individuals suggests that this may be a clinically significant residue (PMID: 1945482, 19258401, 11391798, 22566194). 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.
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000505342 SCV000599539 pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research

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