ClinVar Miner

Submissions for variant NM_018328.4(MBD5):c.3087C>G (p.Asn1029Lys) (rs771343592)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188107 SCV000241714 uncertain significance not provided 2014-09-26 criteria provided, single submitter clinical testing p.Asn1029Lys (N1029K) AAC>AAG: c.3087 C>G in exon 12 of the MBD5 gene (NM_018328.4) The N1029K 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 N1029K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved through mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, to our knowledge, only deletions and frameshift mutations 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 mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Invitae RCV000645279 SCV000767021 uncertain significance Mental retardation, autosomal dominant 1 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 1029 of the MBD5 protein (p.Asn1029Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs771343592, ExAC 0.02%). This variant has not been reported in the literature in individuals with MBD5-related disease. ClinVar contains an entry for this variant (Variation ID: 206093). 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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