ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.527A>G (p.Glu176Gly) (rs201082445)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557702 SCV000630713 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-05-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 176 of the SDHB protein (p.Glu176Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs201082445, ExAC 0.001%). This variant has not been reported in the literature in individuals with SDHB-related disease. ClinVar contains an entry for this variant (Variation ID: 459153). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C1). 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. 5
Ambry Genetics RCV001023850 SCV001185782 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-09 criteria provided, single submitter clinical testing The p.E176G variant (also known as c.527A>G), located in coding exon 5 of the SDHB gene, results from an A to G substitution at nucleotide position 527. The glutamic acid at codon 176 is replaced by glycine, an amino acid with similar properties. This amino acid position is poorly 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.
GeneDx RCV001577591 SCV001804994 uncertain significance not provided 2020-09-01 no assertion criteria provided clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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