ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.488C>T (p.Ser163Phe) (rs769687734)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000466229 SCV000554028 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-10-30 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 163 of the SDHB protein (p.Ser163Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs769687734, ExAC 0.01%). This variant has been reported in an individual affected with gastrointestinal stromal tumor (PMID: 25987131). ClinVar contains an entry for this variant (Variation ID: 412485). 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 RCV000564474 SCV000675081 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-14 criteria provided, single submitter clinical testing The p.S163F variant (also known as c.488C>T), located in coding exon 5 of the SDHB gene, results from a C to T substitution at nucleotide position 488. The serine at codon 163 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration has been identified in the germline of one patient diagnosed with a GIST at age 35 and no family history of paraganglioma (Kang G et al. Oncotarget, 2016 Feb;7:6538-51). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction 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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