ClinVar Miner

Submissions for variant NM_004992.3(MECP2):c.596C>G (p.Pro199Arg) (rs267608502)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000610375 SCV000727611 likely benign not specified 2018-02-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000691182 SCV000818928 uncertain significance Severe neonatal-onset encephalopathy with microcephaly 2018-06-15 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 199 of the MECP2 protein (p.Pro199Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is present in population databases (rs267608502, ExAC 0.01%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with MECP2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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