ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs1340029095
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV003448328 SCV004175921 likely benign Rett syndrome 2023-12-06 reviewed by expert panel curation The p.Leu383Phe variant in MECP2 (NM_004992.4) is observed in at least 2 unaffected individuals (internal database - Invitae) (BS2). This variant is also found in two patients with an alternate molecular basis of disease (internal database - GeneDx) (BP5). The p.Leu383Phe variant is present in 10 XX and 5 XY individuals in gnomAD v4 (0.001%) (not sufficient to meet BS1 criteria). Computational prediction analysis tools are inconclusive for this variant. In summary, the p.Leu395Phe variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS2, BP5).
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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000600874 SCV000919618 uncertain significance not specified 2023-03-14 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. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.8e-06 in 173283 control chromosomes including one female in the gnomAD database. 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. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign (n=2) and VUS (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV001210472 SCV001381961 likely benign Severe neonatal-onset encephalopathy with microcephaly 2024-01-29 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001508974 SCV001715429 uncertain significance not provided 2020-12-08 criteria provided, single submitter clinical testing

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