ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.8C>G (p.Ala3Gly) (rs11203289)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000128921 SCV000172790 benign Hereditary cancer-predisposing syndrome 2014-12-22 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Invitae RCV001079357 SCV000261805 benign Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-11-23 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000368190 SCV000351451 benign Carney-Stratakis syndrome 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000275977 SCV000351452 benign Hereditary Paraganglioma-Pheochromocytoma Syndromes 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx RCV000121999 SCV000514599 benign not specified 2016-11-09 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000121999 SCV000540300 benign not specified 2016-06-23 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000034690 SCV000610498 benign not provided 2017-04-19 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000121999 SCV000859747 benign not specified 2018-03-04 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000755699 SCV000883132 benign Paragangliomas 4 2018-11-21 criteria provided, single submitter clinical testing
Mendelics RCV000986270 SCV001135209 likely benign Gastrointestinal stromal tumor 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000121999 SCV001363919 benign not specified 2019-12-23 criteria provided, single submitter clinical testing Variant summary: SDHB c.8C>G (p.Ala3Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0031 in 242034 control chromosomes in the gnomAD database, including 19 homozygotes. The observed variant frequency is approximately over 3000 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. To our knowledge, no occurrence of c.8C>G in individuals affected with Pheochromocytoma and no experimental evidence demonstrating its impact on protein function have been reported. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign/likely benign, n=7). Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286622 SCV001473226 benign none provided 2020-05-19 criteria provided, single submitter clinical testing
OMIM RCV000013632 SCV000033879 uncertain significance Cowden syndrome 2008-08-01 no assertion criteria provided literature only
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034690 SCV000043487 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
ITMI RCV000121999 SCV000086210 not provided not specified 2013-09-19 no assertion provided reference population

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