ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.593G>C (p.Ser198Thr)

dbSNP: rs1570945857
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000804255 SCV000944155 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2022-10-17 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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. 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 expected to disrupt SDHB protein function. ClinVar contains an entry for this variant (Variation ID: 649342). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 198 of the SDHB protein (p.Ser198Thr).
Ambry Genetics RCV002352375 SCV002647544 uncertain significance Hereditary cancer-predisposing syndrome 2021-03-19 criteria provided, single submitter clinical testing The p.S198T variant (also known as c.593G>C), located in coding exon 6 of the SDHB gene, results from a G to C substitution at nucleotide position 593. The serine at codon 198 is replaced by threonine, an amino acid with similar properties. 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.
All of Us Research Program, National Institutes of Health RCV004803235 SCV005424055 uncertain significance Hereditary pheochromocytoma-paraganglioma 2024-06-09 criteria provided, single submitter clinical testing This missense variant replaces serine with threonine at codon 198 of the SDHB protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SDHB-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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