ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.818C>T (p.Thr273Ile) (rs587781720)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129906 SCV000184724 likely pathogenic Hereditary cancer-predisposing syndrome 2014-09-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Counsyl RCV000409578 SCV000488301 uncertain significance Paragangliomas 5 2016-02-18 criteria provided, single submitter clinical testing
Invitae RCV000649428 SCV000771256 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2018-10-04 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 273 of the SDHA protein (p.Thr273Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs587781720, ExAC 0.009%). This variant has been reported in an individual affected with gastrointestinal stromal tumor (PMID: 23109135). ClinVar contains an entry for this variant (Variation ID: 141401). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance 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.

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.