ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.716C>T (p.Ser239Phe) (rs201098090)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000466110 SCV000554011 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-10-10 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 239 of the SDHB protein (p.Ser239Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs201098090, ExAC 0.02%). This variant has been reported in an individual affected with metastatic paraganglioma (PMID: 18382370). ClinVar contains an entry for this variant (Variation ID: 412475). 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 RCV000570083 SCV000664761 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-08 criteria provided, single submitter clinical testing The p.S239F variant (also known as c.716C>T), located in coding exon 7 of the SDHB gene, results from a C to T substitution at nucleotide position 716. The serine at codon 239 is replaced by phenylalanine, an amino acid with highly dissimilar properties. One study identified this alteration in 1/16 metastatic paragangliomas that were tested for mutations in SDHB and SDHD (Klein RD et al. Diagn. Mol. Pathol. 2008 Jun;17:94-100). 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.
Illumina Clinical Services Laboratory,Illumina RCV001097530 SCV001253819 uncertain significance Hereditary Paraganglioma-Pheochromocytoma Syndromes 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001099287 SCV001255730 uncertain significance Carney-Stratakis syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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