ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.80G>A (p.Arg27Gln)

gnomAD frequency: 0.00001  dbSNP: rs373976827
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219487 SCV000278537 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-26 criteria provided, single submitter clinical testing The p.R27Q variant (also known as c.80G>A), located in coding exon 2 of the SDHB gene, results from a G to A substitution at nucleotide position 80. The arginine at codon 27 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a patient diagnosed with a pheochromocytoma at age 44 (Dénes J et al. J. Clin. Endocrinol. Metab., 2015 Mar;100:E531-41). This amino acid position is highly 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.
Invitae RCV000560433 SCV000630733 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 27 of the SDHB protein (p.Arg27Gln). This variant is present in population databases (rs373976827, gnomAD 0.006%). This missense change has been observed in individual(s) with pheochromocytoma and/or paraganglioma (PMID: 25494863, 34906457). ClinVar contains an entry for this variant (Variation ID: 234049). 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 with a negative predictive value of 95%. 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.
All of Us Research Program, National Institutes of Health RCV000505281 SCV004819916 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-08-08 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 27 of the SDHB protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with pheochromocytoma in the literature (PMID: 25494863). This variant has been identified in 5/250678 chromosomes 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.
Section on Medical Neuroendocrinolgy, National Institutes of Health RCV000505281 SCV000599489 pathogenic Hereditary pheochromocytoma-paraganglioma no assertion criteria provided research

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