ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.488C>T (p.Ser163Phe)

gnomAD frequency: 0.00001  dbSNP: rs769687734
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000466229 SCV000554028 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2022-09-28 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 163 of the SDHB protein (p.Ser163Phe). This variant is present in population databases (rs769687734, gnomAD 0.01%). This missense change has been observed in individual(s) with gastrointestinal stromal tumor (PMID: 25987131). ClinVar contains an entry for this variant (Variation ID: 412485). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDHB protein function. 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 2022-01-31 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 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.

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