ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.170A>G (p.His57Arg) (rs35962811)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129655 SCV000184453 benign Hereditary cancer-predisposing syndrome 2015-11-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Subpopulation frequency in support of benign classification,Other strong data supporting benign classification
Invitae RCV000513898 SCV000287761 benign not provided 2019-03-06 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000301812 SCV000351427 likely benign Pheochromocytoma 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000358920 SCV000351428 likely benign Paraganglioma and gastric stromal sarcoma 2016-06-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000122000 SCV000540303 likely benign not specified 2016-03-28 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: 2 papers describe as non disease causing; ExAC: 0.8% (79/10404) African chromosomes; ClinVar: 3 labs classify as LB
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000513898 SCV000609975 likely benign not provided 2017-05-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000513898 SCV000886094 likely benign not provided 2018-03-22 criteria provided, single submitter clinical testing The SDHB c.170A>G; p.His57Arg variant is reported in the medical literature with an individual with Cowden or Cowden-like syndrome (Ni 2012), but is also reported at a greater frequency in the general population than expected for the disorder (Olfson 2015). The variant is described as benign or likely benign by several sources in the ClinVar database (Variation ID: 135192). This variant is found in the African population with an overall allele frequency of 0.8% (191/24040 alleles) in the Genome Aggregation Database. The amino acid at this position is weakly conserved across species and computational algorithms (PolyPhen-2, SIFT) predict this variant is tolerated. Considering available information, this variant is classified as likely benign. References: Ni Y et al. Germline SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like syndrome via FAD/NAD-dependant destabilization of p53. Hum Mol Genet. 2012 Jan 15;21(2):300-10. Olfson E et al. Identification of Medically Actionable Secondary Findings in the 1000 Genomes. PLoS One. 2015 Sep 2;10(9):e0135193.
Integrated Genetics/Laboratory Corporation of America RCV000122000 SCV000918202 benign not specified 2017-12-04 criteria provided, single submitter clinical testing Variant summary: The SDHB c.170A>G (p.His57Arg) variant involves the alteration of a non-conserved nucleotide located in the Succinate dehydogenase/fumarate reductase N-terminal (IPR025192) and the 2Fe-2S ferredoxin-type iron-sulfur binding domains (IPR001041) (InterPro). 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 222/278486 control chromosomes (gnomAD and Bodian_2014) at a frequency of 0.0007972, which is approximately 911 times the estimated maximal expected allele frequency of a pathogenic SDHB variant (0.0000009), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in individuals with Hereditary paraganglioma-pheochromocytoma syndrome via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
ITMI RCV000122000 SCV000086211 not provided not specified 2013-09-19 no assertion provided reference population
CSER _CC_NCGL, University of Washington RCV000148867 SCV000190611 likely benign Cowden syndrome 2014-06-01 no assertion criteria provided research

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