ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.80G>A (p.Arg27Gln) (rs373976827)

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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 RCV000219487 SCV000278537 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-05 criteria provided, single submitter clinical testing The p.R27Q variant (also known as c.80G>A), located in coding exon 2 of the SDHB gene, results from a G to A substitution at nucleotide position 80. The arginine at codon 27 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a patient diagnosed with a pheochromocytoma at age 44 (Dénes J et al. J. Clin. Endocrinol. Metab., 2015 Mar;100:E531-41). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000560433 SCV000630733 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 27 of the SDHB protein (p.Arg27Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs373976827, ExAC 0.006%). This variant has been reported in an individual affected with pheochromocytoma (PMID: 25494863). ClinVar contains an entry for this variant (Variation ID: 234049). 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 tolerated, 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.
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000505281 SCV000599489 pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research

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