ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.14T>G (p.Val5Gly) (rs760565241)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547089 SCV000630692 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-09-02 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 5 of the SDHB protein (p.Val5Gly). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glycine. This variant is present in population databases (rs760565241, ExAC 0.002%). This variant has been reported in an individual affected with pheochromocytoma (PMID: 28229225). ClinVar contains an entry for this variant (Variation ID: 459136). 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.
Ambry Genetics RCV001011890 SCV001172272 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-14 criteria provided, single submitter clinical testing The p.V5G variant (also known as c.14T>G), located in coding exon 1 of the SDHB gene, results from a T to G substitution at nucleotide position 14. The valine at codon 5 is replaced by glycine, an amino acid with dissimilar properties. In one study, this alteration was detected in 1/48 pheochromocytoma patients (Maignan A et al. Langenbecks Arch Surg, 2017 Aug;402:787-798). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction by BayesDel for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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