ClinVar Miner

Submissions for variant NM_018328.4(MBD5):c.644G>A (p.Arg215His) (rs771325235)

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 RCV000188069 SCV000241673 uncertain significance not provided 2016-10-18 criteria provided, single submitter clinical testing p.Arg215His (CGT>CAT): c.644 G>A in exon 9 of the MBD5 gene (NM_018328.4) The Arg215His variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Arg215His variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species; however, to our knowledge, only deletions and frameshift mutations in MBD5 have been published in association with epilepsy. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Invitae RCV000645277 SCV000767019 uncertain significance Mental retardation, autosomal dominant 1 2017-12-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 215 of the MBD5 protein (p.Arg215His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs771325235, ExAC 0.002%). This variant has not been reported in the literature in individuals with MBD5-related disease. ClinVar contains an entry for this variant (Variation ID: 206060). 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.