ClinVar Miner

Submissions for variant NM_018328.4(MBD5):c.935A>T (p.Lys312Ile) (rs146031838)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188076 SCV000241680 uncertain significance not specified 2013-11-14 criteria provided, single submitter clinical testing p.Lys312Ile (AAA>ATA): c.935 A>T in exon 9 of the MBD5 gene (NM_018328.4) The Lys312Ile missense change in the MBD5 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. This variant is a non-conservative amino acid substitution of a positively charged Lysine residue with an uncharged, non-polar Isoleucine residue at a position that is conserved in mammals but is not conserved in more distantly related species. To our knowledge, only deletions and frameshift mutations in MBD5 have been published in association with epilepsy. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Lys312Ile is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000645267 SCV000767009 uncertain significance Mental retardation, autosomal dominant 1 2017-11-10 criteria provided, single submitter clinical testing This sequence change replaces lysine with isoleucine at codon 312 of the MBD5 protein (p.Lys312Ile). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and isoleucine. This variant is present in population databases (rs146031838, ExAC 0.05%). This variant has not been reported in the literature in individuals with MBD5-related disease. ClinVar contains an entry for this variant (Variation ID: 206066). 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: "Possibly Damaging"; 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.

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