ClinVar Miner

Submissions for variant NM_018328.4(MBD5):c.1234G>A (p.Val412Ile) (rs761118931)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484879 SCV000569187 uncertain significance not specified 2017-10-06 criteria provided, single submitter clinical testing The V412I variant in the MBD5 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V412I variant is observed in 4/10396 (0.04%) alleles from individuals of African background, in the ExAC dataset (Lek et al., 2016). The V412I 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 where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V412I as a variant of uncertain significance.
Invitae RCV000549902 SCV000645777 uncertain significance Mental retardation, autosomal dominant 1 2018-10-22 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 412 of the MBD5 protein (p.Val412Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs761118931, ExAC 0.04%). This variant has not been reported in the literature in individuals with MBD5-related disease. ClinVar contains an entry for this variant (Variation ID: 420374). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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.

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