Submissions for variant NM_003001.3(SDHC):c.20+11_20+12dup

dbSNP: rs35215598

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037724	SCV000061386	benign	not specified	2013-11-05	criteria provided, single submitter	clinical testing	20+11_20+12dupTG in intron 1 of SDHC: This variant has been identified in 15% ( 63/420) of patients with hereditary paraganglioma and in 6% (11/200) of controls (Burnichon 2009). This variant is also annotated as a common polymorphism in db SNP and but has been identified in 6% (516/8254) of European American chromosome s and 21% (889/4266) of African American chromosomes by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS/; dbSNP rs27118366). This variant i s located in the 5' splice region and computational tools do not suggest an impa ct to splicing. However, this information is not predictive enough to rule out p athogenicity. In summary, these data support that the 20+11_20+12dupTG variant i s benign based on frequency data.
PreventionGenetics, part of Exact Sciences	RCV000037724	SCV000309337	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000399693	SCV000350261	benign	Pheochromocytoma	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000351164	SCV000482987	benign	Charcot-Marie-Tooth, Intermediate	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000354800	SCV000482988	benign	Charcot-Marie-Tooth disease type 4E	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000297715	SCV000482989	benign	Roussy-Lévy syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000354800	SCV000482990	benign	Charcot-Marie-Tooth disease type 4E	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000397974	SCV000482991	benign	Charcot-Marie-Tooth disease, type I	2016-06-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000492358	SCV000581215	benign	Hereditary cancer-predisposing syndrome	2015-07-08	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	RCV000587490	SCV000698137	benign	not provided	2016-05-25	criteria provided, single submitter	clinical testing	Variant summary: The SDHC c.20+11_20+12dupTG is an intronic variant at a position not widely known to affect splicing. One in silico tool (MutationTaster) predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant change to the normal splicing. This variant was found in 12727/120920 control chromosomes (including 891 homozygotes) at a frequency of 0.1052514, which is approximately 673609 times the estimated maximal expected allele frequency of a pathogenic SDHC variant (0.0000002), suggesting this variant is a common benign polymorphism. In addition, one clinical diagnostic laboratory classified this variant as benign. Taken together, based on the allele frequency in the general population, this variant is classified as Benign.
Invitae	RCV001521360	SCV001730692	benign	Gastrointestinal stromal tumor; Paragangliomas 3	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000587490	SCV001846279	benign	not provided	2018-09-25	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587490	SCV002048066	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing