ClinVar Miner

Submissions for variant NM_018328.4(MBD5):c.3385T>C (p.Ser1129Pro) (rs200395037)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188133 SCV000241740 uncertain significance not provided 2015-12-24 criteria provided, single submitter clinical testing The S1129P variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The S1129P variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The S1139P 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 highly conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, to our knowledge, only loss-of-function 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.
Illumina Clinical Services Laboratory,Illumina RCV000305222 SCV000416712 uncertain significance Intellectual Disability, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000686863 SCV000814402 uncertain significance Mental retardation, autosomal dominant 1 2018-06-13 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 1129 of the MBD5 protein (p.Ser1129Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is present in population databases (rs200395037, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with MBD5-related disease. ClinVar contains an entry for this variant (Variation ID: 206117). 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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