Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001110792.2(MECP2):c.408G>C (p.Leu136Phe)

Curation Version - 1.0
Curation History
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CA270369

143549 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 40db135c-d0c1-40a2-bb59-8540e334e2d5

Approved on: 2022-10-11

Published on: 2022-12-02

HGVS expressions

NM_001110792.2:c.408G>C

NM_001110792.2(MECP2):c.408G>C (p.Leu136Phe)

NC_000023.11:g.154032212C>G

CM000685.2:g.154032212C>G

NC_000023.10:g.153297663C>G

CM000685.1:g.153297663C>G

NC_000023.9:g.152950857C>G

NG_007107.2:g.109916G>C

NG_007107.3:g.109892G>C

ENST00000303391.11:c.372G>C

ENST00000453960.7:c.408G>C

ENST00000637917.1:n.5G>C

ENST00000303391.10:c.372G>C

ENST00000369957.5:c.*426G>C

ENST00000407218.5:c.408G>C

ENST00000453960.6:c.408G>C

ENST00000486506.5:n.2720G>C

ENST00000611468.1:c.360G>C

ENST00000619732.4:c.372G>C

ENST00000622433.4:c.360G>C

ENST00000628176.2:c.372G>C

NM_001110792.1:c.408G>C

NM_001316337.1:c.93G>C

NM_004992.3:c.372G>C

NM_001316337.2:c.93G>C

NM_001369391.2:c.93G>C

NM_001369392.2:c.93G>C

NM_001369393.2:c.93G>C

NM_001369394.1:c.93G>C

NM_001369394.2:c.93G>C

NM_001386137.1:c.-189G>C

NM_001386138.1:c.-189G>C

NM_001386139.1:c.-189G>C

NM_004992.4:c.372G>C

Pathogenic

PS3_Supporting PS1 PM1 PM6 PM2_Supporting

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The c.372G>C (p.Leu124Phe) variant in MECP2 (NM_004992.3) occurs in the de novo state (biological parentage unconfirmed) in an individual with Rett syndrome (PMID 10991688) (PM6). The c.372G>C (p.Leu124Phe) variant occurs in the well-characterized methyl-DNA binding functional domain of the MECP2 gene (PM1). The c.372G>C (p.Leu124Phe) variant in MECP2 is absent from gnomAD (PM2_supporting). MECP2 heterochromatin binding assay and in vitro transcriptional repression assay have shown that this variant impacts protein function (PMID 12843318) (PS3_supporting). The c.372G>T variant in the MECP2 gene results in a p.Leu124Phe change that is a previously established pathogenic variant (internal database - Invitae) (PS1). In summary, the c.372G>C (p.Leu124Phe) variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS1, PM1, PM6, PM2_supporting, PS3_supporting).

PS3_Supporting

MECP2 heterochromatin binding assay and in vitro transcriptional repression assay have shown that this variant impacts protein function (PMID 12843318) (PS3_supporting).

PS1

The c.372G>T variant in the MECP2 gene results in a p.Leu124Phe change that is a previously established pathogenic variant (internal database - Invitae) (PS1).

PM1

The p.Leu124Phe variant occurs in the well-characterized methyl-DNA binding functional domain of the MECP2 gene (PM1).

PM6

The p.Leu124Phe variant in MECP2 occurs in the de novo state (biological parentage unconfirmed) in an individual with Rett syndrome (PMID 10991688) (PM6).

PM2_Supporting

The p.Leu124Phe variant in MECP2 is absent from gnomAD (PM2_supporting).

Curation History

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