ClinVar Miner

Submissions for variant NM_004992.3(MECP2):c.1163C>T (p.Pro388Leu) (rs61753006)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000693901 SCV000822324 uncertain significance Severe neonatal-onset encephalopathy with microcephaly 2018-03-28 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 388 of the MECP2 protein (p.Pro388Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs61753006, ExAC <0.01%), including at least one homozygous and/or hemizygous individual. This variant has been reported in an individual affected with Rett syndrome (PMID: 11960578). ClinVar contains an entry for this variant (Variation ID: 143398). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. A different missense substitution at this codon (p.Pro388Thr) has been reported in an individual affected with Rett syndrome (PMID: 12449561). 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.
RettBASE RCV000132924 SCV000187905 uncertain significance Rett syndrome 2010-07-13 no assertion criteria provided curation

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