ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.455C>T (p.Ser152Phe) (rs200414835)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459898 SCV000554039 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2019-12-17 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 152 of the SDHB protein (p.Ser152Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs200414835, ExAC 0.07%). This variant has been reported in an individual with a head and neck paraganglioma (PMID: 26269449). ClinVar contains an entry for this variant (Variation ID: 412492). 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 C35"). 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 RCV000572596 SCV000664481 uncertain significance Hereditary cancer-predisposing syndrome 2020-07-15 criteria provided, single submitter clinical testing The p.S152F variant (also known as c.455C>T), located in coding exon 5 of the SDHB gene, results from a C to T substitution at nucleotide position 455. The serine at codon 152 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration has been reported as a variant of uncertain significance in a cohort of 329 individuals with a personal history of pheochromocytoma and/or paraganglioma (PPGL), with no syndromic and no PPGL family history (Currás-Freixes M et al. J. Med. Genet. 2015 Oct;52:647-56). This amino acid position is well 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.
Fulgent Genetics,Fulgent Genetics RCV000763772 SCV000894674 uncertain significance Carney-Stratakis syndrome; Paragangliomas 4; Pheochromocytoma 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001591104 SCV001825487 uncertain significance not provided 2021-10-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26269449)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001764453 SCV002010045 uncertain significance Paragangliomas 4 2021-11-03 criteria provided, single submitter clinical testing

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