ClinVar Miner

Submissions for variant NM_018328.4(MBD5):c.19T>A (p.Cys7Ser) (rs766104877)

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 RCV000412834 SCV000492330 uncertain significance not specified 2016-12-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MBD5 gene. The C7S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The C7S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The C7S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Additionally, to our knowledge, only loss-of-function pathogenic variants in MBD5 have been published in association with epilepsy. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000817602 SCV000958171 uncertain significance Mental retardation, autosomal dominant 1 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces cysteine with serine at codon 7 of the MBD5 protein (p.Cys7Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is present in population databases (rs766104877, ExAC 0.001%). This variant has not been reported in the literature in individuals with MBD5-related conditions. ClinVar contains an entry for this variant (Variation ID: 373711). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "unavailable"; Align-GVGD: "Class C0"). 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.