Submissions for variant NM_003000.3(SDHB):c.487T>C (p.Ser163Pro)

gnomAD frequency: 0.00921  dbSNP: rs33927012

Total submissions: 29

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000132153	SCV000187226	benign	Hereditary cancer-predisposing syndrome	2014-12-23	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.
GeneDx	RCV000034688	SCV000235633	benign	not provided	2018-04-10	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 19215943, 16322339, 17298551, 16912137, 22995991, 19768395, 22584711, 19802898, 19399650, 22293219, 24735130, 20981092, 27153395, 18678321, 21979946, 25376524, 22938532, 22703879, 25694510, 23666964, 25333069, 24728327, 26071763, 17102082, 17102083, 22270996, 25695889, 17639058, 14985401, 26182300, 18419787, 19153209, 19522823, 19454582, 27279923, 27884173, 26092435, 28374168, 29386252, 30050099, 31019283)
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202946	SCV000257933	benign	Paragangliomas 4	2015-02-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206861	SCV000262194	benign	Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000122002	SCV000309334	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000282667	SCV000351418	benign	Hereditary pheochromocytoma-paraganglioma	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.
Counsyl	RCV000202946	SCV000488422	benign	Paragangliomas 4	2016-03-23	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000122002	SCV000596998	benign	not specified	2018-04-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000122002	SCV000605078	likely benign	not specified	2018-08-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000122002	SCV000698135	benign	not specified	2017-05-08	criteria provided, single submitter	clinical testing	Variant summary: The SDHB c.487T>C (p.Ser163Pro) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 1523/121404 control chromosomes (21 homozygotes) at a frequency of 0.0125449, which largely exceeds 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. Taken together, this variant is classified as benign.
Eurofins Ntd Llc (ga)	RCV000122002	SCV000702933	benign	not specified	2016-11-16	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000202946	SCV000782276	uncertain significance	Paragangliomas 4	2016-11-01	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000202946	SCV000883134	uncertain significance	Paragangliomas 4	2018-11-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000986263	SCV001135202	likely benign	Gastrointestinal stromal tumor	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034688	SCV001147171	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	SDHB: BS1, BS2
Illumina Laboratory Services, Illumina	RCV001099292	SCV001255735	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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034688	SCV002010044	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000132153	SCV002527080	benign	Hereditary cancer-predisposing syndrome	2020-09-11	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000122002	SCV002552130	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000202946	SCV004045350	benign	Paragangliomas 4	2023-04-24	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
Color Diagnostics, LLC DBA Color Health	RCV000202946	SCV004362272	benign	Paragangliomas 4	2022-06-09	criteria provided, single submitter	clinical testing
OMIM	RCV000013633	SCV000033880	uncertain significance	Cowden syndrome	2008-08-01	no assertion criteria provided	literature only
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034688	SCV000043485	no known pathogenicity	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Benign.
ITMI	RCV000122002	SCV000086213	not provided	not specified	2013-09-19	no assertion provided	reference population
Center of Medical Genetics and Primary Health Care	RCV001269360	SCV001448699	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000122002	SCV001743804	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000122002	SCV001807023	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000122002	SCV001922351	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000122002	SCV001959772	benign	not specified		no assertion criteria provided	clinical testing