Submissions for variant NM_003002.4(SDHD):c.204C>T (p.Ser68=)

gnomAD frequency: 0.11428  dbSNP: rs9919552

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine	RCV000037727	SCV000061389	benign	not specified	2012-12-21	criteria provided, single submitter	clinical testing	This variant is classified as benign because it does not change the amino acid a nd is frequent in the general population (rs9919552, MAF >1%). Noted as 2.8-4.4% in TCA gene mutation database.
Ambry Genetics	RCV000162450	SCV000212803	benign	Hereditary cancer-predisposing syndrome	2014-11-21	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
PreventionGenetics,PreventionGenetics	RCV000037727	SCV000309338	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000265027	SCV000367347	benign	Pheochromocytoma	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV002228123	SCV000563767	benign	Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3	2021-12-17	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV000587940	SCV000605084	benign	not provided	2021-12-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587940	SCV000698140	benign	not provided	2016-05-25	criteria provided, single submitter	clinical testing	Variant summary: The SDHD c.204C>T (p.Ser68Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. This variant was found in 4824/121320 control chromosomes (622 homozygotes), predominantly observed in the African subpopulation (610 homozygotes) at a frequency of 0.3507319 (3642/10384). This frequency is greatly exceeds the estimated maximal expected allele frequency of a pathogenic SDHD variant (0.0000016), suggesting this is a common benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories have classified this variant as Benign/Likely Benign. Taken together, this variant is classified as Benign.
GeneDx	RCV000587940	SCV001944511	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001807015	SCV002054703	benign	Mitochondrial complex 2 deficiency, nuclear type 3	2021-07-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001807014	SCV002054704	benign	Paragangliomas 1	2021-07-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000265027	SCV002054705	benign	Pheochromocytoma	2021-07-15	criteria provided, single submitter	clinical testing
Sema4,Sema4	RCV000162450	SCV002527120	benign	Hereditary cancer-predisposing syndrome	2019-12-09	criteria provided, single submitter	curation
Genetic Services Laboratory,University of Chicago	RCV000037727	SCV000194885	likely benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000037727	SCV001740246	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000037727	SCV001930266	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000037727	SCV001959655	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000037727	SCV002036847	benign	not specified		no assertion criteria provided	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000037727	SCV002549994	likely benign	not specified	2021-12-29	no assertion criteria provided	clinical testing