Submissions for variant NM_003002.4(SDHD):c.312C>T (p.His104=)

gnomAD frequency: 0.00690  dbSNP: rs61734352

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000192473	SCV000248839	benign	not specified	2017-11-08	criteria provided, single submitter	clinical testing
Invitae	RCV002229021	SCV000262371	benign	Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000303724	SCV000367348	likely benign	Pheochromocytoma	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000192473	SCV000525133	benign	not specified	2017-12-06	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.
Ambry Genetics	RCV000561501	SCV000664476	benign	Hereditary cancer-predisposing syndrome	2015-10-09	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586378	SCV000698142	benign	not provided	2016-05-25	criteria provided, single submitter	clinical testing	Variant summary: The SDHD c.312C>T (p.His104His) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 260/121396 control chromosomes (including 3 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0238599 (248/10394). This frequency greatly exceeds the estimated maximal expected allele frequency of a pathogenic SDHD variant (0.0000016), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories have classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000192473	SCV000884503	benign	not specified	2018-07-12	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000586378	SCV000889833	benign	not provided	2020-09-09	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002485291	SCV002801255	likely benign	Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Mitochondrial complex 2 deficiency, nuclear type 3	2022-05-24	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316088	SCV004015428	benign	Paragangliomas 3	2023-07-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV003507266	SCV004362303	benign	Paragangliomas 1	2022-10-20	criteria provided, single submitter	clinical testing