ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.335C>T (p.Thr112Ile) (rs199869408)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228547 SCV000287824 uncertain significance Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 112 of the SDHD protein (p.Thr112Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs199869408, ExAC 0.01%). This variant has been reported in an individual affected with pheochromocytoma (PMID: 17102085). This variant did not appear to segregate with disease in one extended family; it was reported in multiple apparently unaffected individuals in the family, including an individual who inherited this variant in trans with a known pathogenic SDHD variant, p.Gln109* (referred to as Q109X). In addition, the sole affected individual in the family did not carry this variant but did have the p.Gln109* variant (PMID: 17102085, 1606155). Also, the variant has been observed in two individuals affected with papillary thyroid cancer. ClinVar contains an entry for this variant (Variation ID: 239468). Experimental studies in a yeast model system showed that this variant does not affect oxidative growth but does result in a reduction of SDH enzyme activity and an increase in mtDNA mutability (PMID: 23175444). The clinical significance of these findings is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000455598 SCV000540307 uncertain significance not specified 2016-06-16 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 family that also carried Q109X, and T112I did not segregate with disease.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000455598 SCV000602186 uncertain significance not specified 2017-05-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760070 SCV000889835 uncertain significance not provided 2018-03-06 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764954 SCV000896127 uncertain significance Carney-Stratakis syndrome; Pheochromocytoma; Mitochondrial complex II deficiency; Paragangliomas 1 2018-10-31 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000455598 SCV000923664 uncertain significance not specified 2019-01-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV001020081 SCV001181512 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-27 criteria provided, single submitter clinical testing Insufficient evidence

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.