ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.268C>G (p.Arg90Gly) (rs74315366)

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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 RCV000165299 SCV000216018 uncertain significance Hereditary cancer-predisposing syndrome 2014-08-05 criteria provided, single submitter clinical testing The p.R90G variant (also known as c.268C>G), located in coding exon 3 of the SDHB gene, results from a C to G substitution at nucleotide position 268. The arginine at codon 90 is replaced by glycine, an amino acid with dissimilar properties. Another amino acid substitution at codon 90, p.R90Q, has been reported in multiple paraganglioma kindreds to date (Castellano et al. Ann NY Acad Sci 2006 Aug; 1073:156-65; Neumann et al. Cancer Res 2009 Apr15; 69(8). Supplementary table1; http://chromium.liacs.nl/lovd_sdh/variants.php). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001217636 SCV001389483 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2019-05-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 90 of the SDHB protein (p.Arg90Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 185809). 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. 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.

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