ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.158G>A (p.Gly53Glu)

gnomAD frequency: 0.00041  dbSNP: rs34916635
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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163315 SCV000213843 benign Hereditary cancer-predisposing syndrome 2015-09-06 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001081765 SCV000261941 benign Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2024-02-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000266464 SCV000351429 likely benign Carney-Stratakis syndrome 2019-04-21 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000323978 SCV000351430 likely benign Hereditary pheochromocytoma-paraganglioma 2019-04-21 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx RCV000713176 SCV000730537 likely benign not provided 2020-08-25 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 23512077, 25694510, 21979946, 25394176, 19802898, 18458953, 23072324, 20923864, 28873162, 30152102)
Athena Diagnostics RCV000713176 SCV000843759 benign not provided 2018-01-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000602372 SCV001478595 benign not specified 2021-01-17 criteria provided, single submitter clinical testing Variant summary: SDHB c.158G>A (p.Gly53Glu) results in a non-conservative amino acid change located in the 2Fe-2S ferredoxin-type iron-sulfur binding domain (IPR010141) of 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 0.00053 in 251378 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is higher than the estimated maximal expected allele frequency for a pathogenic variant in SDHB causing Hereditary Paraganglioma-Pheochromocytoma Syndrome phenotype (2.2e-07), strongly suggesting that the variant is benign. Although, this variant has been reported in the literature (example, Fishbein_2013, Cox_2018), to our knowledge, no occurrence of c.158G>A in individuals affected with Hereditary Paraganglioma-Pheochromocytoma Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five 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 benign (n=3)/likely benign (n=2). Based on the evidence outlined above, the variant was classified as benign.
Sema4, Sema4 RCV000163315 SCV002527060 benign Hereditary cancer-predisposing syndrome 2021-07-15 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000602372 SCV002552241 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000713176 SCV004220332 benign not provided 2018-01-08 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV003514320 SCV004362281 benign Paragangliomas 4 2022-09-20 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000713176 SCV004700590 likely benign not provided 2024-04-01 criteria provided, single submitter clinical testing SDHB: BS2
PreventionGenetics, part of Exact Sciences RCV004535070 SCV004743598 likely benign SDHB-related disorder 2020-07-13 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
GenomeConnect, ClinGen RCV000709876 SCV000840213 not provided Gastrointestinal stromal tumor; Carney-Stratakis syndrome; Paragangliomas 4; Pheochromocytoma; Cowden syndrome 1 no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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