ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.563G>A (p.Arg188Gln) (rs139881415)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000518854 SCV000619459 uncertain significance not provided 2018-06-06 criteria provided, single submitter clinical testing TThe R188Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. A different missense variant at this same codon (R188W) has been reported in an individual with a gastric gastrointestinal stromal tumor; however, additional clinical information and information regarding parental testing was not provided (Miettinen et al., 2013). The R188Q variant is observed in 3/24030 (0.01%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). The R188Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000531381 SCV000651447 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2018-11-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 188 of the SDHA protein (p.Arg188Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs139881415, ExAC 0.02%). This variant has not been reported in the literature in individuals with SDHA-related disease. ClinVar contains an entry for this variant (Variation ID: 450839). 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.