ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.187_188TC[2] (p.Leu64fs) (rs387906358)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481193 SCV000568556 pathogenic not provided 2016-07-25 criteria provided, single submitter clinical testing This deletion of two nucleotides in SDHD is denoted c.191_192delTC at the cDNA level and p.Leu64ProfsX4 (L64PfsX4) at the protein level. The normal sequence, with the bases that are deleted in braces, is TCTC[TC]CACT. The deletion causes a frameshift which changes a Leucine to a Proline at codon 64, and creates a premature stop codon at position 4 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. SDHD c.191_192delTC tracked with disease in a large Australian family with hereditary paraganglioma (Badenhop 2001), and has been reported in multiple individuals with paraganglioma, including those with an apparently sporadic tumor (Burnichon 2009, Neumann 2009, Jafri 2013, Curras-Freixes 2015). We consider this variant to be pathogenic.
Invitae RCV000641035 SCV000762653 pathogenic Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2017-12-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu64Profs*4) in the SDHD gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported  in the literature in individuals and families affected with paraganglioma, and segregates with disease in at lease one family (PMID: 11391796, 15235042, 19454582, 23902947). ClinVar contains an entry for this variant (Variation ID: 6904). Loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001013655 SCV001174270 pathogenic Hereditary cancer-predisposing syndrome 2018-10-17 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
OMIM RCV000007313 SCV000027510 pathogenic Paragangliomas 1 with sensorineural hearing loss 2001-07-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.