ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1183C>T (p.Leu395Phe) (rs1340029095)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000600874 SCV000728725 likely benign not specified 2017-03-14 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.
Integrated Genetics/Laboratory Corporation of America RCV000600874 SCV000919618 uncertain significance not specified 2018-04-16 criteria provided, single submitter clinical testing Variant summary: MECP2 c.1147C>T (p.Leu383Phe) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.9e-06 in 170000 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1147C>T in individuals affected with Rett Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV001210472 SCV001381961 uncertain significance Severe neonatal-onset encephalopathy with microcephaly 2019-06-29 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 383 of the MECP2 protein (p.Leu383Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MECP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 516184). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably 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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