ClinVar Miner

Submissions for variant NM_018328.4(MBD5):c.422G>A (p.Arg141Gln) (rs200245855)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000717904 SCV000848764 likely benign History of neurodevelopmental disorder 2017-05-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,Does not segregate with disease in family study (genes with incomplete penetrance)
GeneDx RCV000522311 SCV000617984 uncertain significance not provided 2017-07-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MBD5 gene. The R141Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R141Q variant is observed in 1/11320 (0.01%) alleles from individuals of Latino background in the Exome Aggregation Consortium (ExAC) data set (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). R141Q has also been observed in several unaffected adults tested at GeneDx. The R141Q 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 where amino acids with similar properties to Arginine 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. 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.

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