Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Integrated Genetics/Laboratory Corporation of America | RCV000607044 | SCV000053116 | likely benign | not specified | 2018-03-02 | criteria provided, single submitter | clinical testing | Variant summary: SDHB c.32G>A (p.Arg11His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00048 in 104928 control chromosomes. The observed variant frequency is approximately 544 fold of the estimated maximal expected allele frequency for a pathogenic variant in SDHB causing Pheochromocytoma phenotype (8.8e-07), strongly suggesting that the variant is benign. c.32G>A has been reported in the literature in individuals affected with eosinophilic chromophobe renal cell carcinoma. These report(s) do not provide unequivocal conclusions about association of the variant with Pheochromocytoma. One publication reports experimental evidence indicating positive SDHB immunostaining in tumors harboring this variant without concommitant pathogenic SDH-gene mutations. However, this does not allow convincing conclusions about the variant effect. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
Invitae | RCV000232749 | SCV000287771 | benign | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2019-12-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000568010 | SCV000675059 | likely benign | Hereditary cancer-predisposing syndrome | 2018-10-01 | criteria provided, single submitter | clinical testing | Other data supporting benign classification;In silico models in agreement (benign);Subpopulation frequency in support of benign classification |
Gene |
RCV000607044 | SCV000730538 | likely benign | not specified | 2018-02-16 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Counsyl | RCV000662963 | SCV000785936 | likely benign | Paragangliomas 4 | 2018-01-16 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000986269 | SCV001135208 | likely benign | Gastrointestinal stromal tumor | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Cancer Variant Interpretation Group UK, |
RCV001253761 | SCV001429630 | likely benign | Pheochromocytoma; Paraganglioma | 2020-07-10 | criteria provided, single submitter | clinical testing | This variant has been observed in a 52-year-old proband diagnosed with three primary renal cell carcinomas, bilateral disease, multiple renal cysts and single angiomyolipoma. This variant has also been observed in three unrelated (to our knowledge) diagnostic cases of PP/PGL (one of which has inner ear PGL). This variant has previously been reported in the literature in patients with bilateral renal cell carcinoma (PMID: 18728283) and neuroendocrine tumour (PMID: 19576851). Succinate:Fumarate ratio in tumour samples from a patient with this variant were observed to be within normal range, indicating neutral impact on protein function (PMID: 30050099) (BS3_supporting). This variant has been observed in 149/274308 total alleles in gnomAD; including 133/24062 African alleles (BS1_strong). Data included in classification: Functional data and control (gnomAD) data Data not included in classification: Incidence in literature and other reported probands In silico predictions (conflicting) |
CSER _CC_NCGL, |
RCV000148868 | SCV000190612 | uncertain significance | Renal cell carcinoma, papillary, 1 | 2014-06-01 | no assertion criteria provided | research | |
Section on Medical Neuroendocrinolgy, |
RCV000505348 | SCV000599482 | pathogenic | Hereditary Paraganglioma-Pheochromocytoma Syndromes | no assertion criteria provided | research |