ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.716C>G (p.Ser239Cys) (rs201098090)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000795778 SCV000935252 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-07-26 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 239 of the SDHB protein (p.Ser239Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs201098090, ExAC 0.02%). This variant has been observed in individual(s) with pheochromocytoma and with breast cancer (PMID: 22270996, 31780696). ClinVar contains an entry for this variant (Variation ID: 161385). 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.
Ambry Genetics RCV001026110 SCV001188429 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-07 criteria provided, single submitter clinical testing The p.S239C variant (also known as c.716C>G), located in coding exon 7 of the SDHB gene, results from a C to G substitution at nucleotide position 716. The serine at codon 239 is replaced by cysteine, an amino acid with dissimilar properties. This alteration has been reported in a woman diagnosed with a pheochromocytoma at age 25 in a Western Swedish cohort of patients with apparently sporadic pheochromocytomas or paragangliomas (Muth A et al. World J Surg, 2012 Jun;36:1389-94). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CSER _CC_NCGL, University of Washington RCV000148869 SCV000190613 uncertain significance Pheochromocytoma 2014-06-01 no assertion criteria provided research

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