ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1135C>T (p.Arg379Cys) (rs749309213)

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 RCV000214185 SCV000274554 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514432 SCV000610367 uncertain significance not provided 2017-05-11 criteria provided, single submitter clinical testing
Invitae RCV000459361 SCV000553873 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2018-12-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 379 of the SDHA protein (p.Arg379Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs749309213, ExAC 0.003%). This variant has not been reported in the literature in individuals with SDHA-related disease. ClinVar contains an entry for this variant (Variation ID: 230873). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.