Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_001110792.2(MECP2):c.408G>T (p.Leu136Phe)

CA270371

143550 (ClinVar)

Gene: MECP2
Condition: Rett syndrome
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 217fc1a3-cebb-449b-9d62-7b2a58d3f29b
Approved on: 2022-10-11
Published on: 2022-12-02

HGVS expressions

NM_001110792.2:c.408G>T
NM_001110792.2(MECP2):c.408G>T (p.Leu136Phe)
NC_000023.11:g.154032212C>A
CM000685.2:g.154032212C>A
NC_000023.10:g.153297663C>A
CM000685.1:g.153297663C>A
NC_000023.9:g.152950857C>A
NG_007107.2:g.109916G>T
NG_007107.3:g.109892G>T
ENST00000303391.11:c.372G>T
ENST00000453960.7:c.408G>T
ENST00000637917.1:n.5G>T
ENST00000303391.10:c.372G>T
ENST00000369957.5:c.*426G>T
ENST00000407218.5:c.408G>T
ENST00000453960.6:c.408G>T
ENST00000486506.5:n.2720G>T
ENST00000611468.1:c.360G>T
ENST00000619732.4:c.372G>T
ENST00000622433.4:c.360G>T
ENST00000628176.2:c.372G>T
NM_001110792.1:c.408G>T
NM_001316337.1:c.93G>T
NM_004992.3:c.372G>T
NM_001316337.2:c.93G>T
NM_001369391.2:c.93G>T
NM_001369392.2:c.93G>T
NM_001369393.2:c.93G>T
NM_001369394.1:c.93G>T
NM_001369394.2:c.93G>T
NM_001386137.1:c.-189G>T
NM_001386138.1:c.-189G>T
NM_001386139.1:c.-189G>T
NM_004992.4:c.372G>T
More

Pathogenic

Met criteria codes 4
PS1 PS2 PM1 PM2_Supporting
Not Met criteria codes 3
PS3 PP4 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The c.372G>T (p.Leu124Phe) variant in MECP2 (NM_004992.3) occurs in the mosaic state in a male patient with a neurodevelopmental phenotype consistent with the MECP2 gene (internal database - Invitae) and therefore confirmed to be de novo (PS2). The c.372G>T (p.Leu124Phe) variant occurs in the well-characterized methyl-DNA binding functional domain of the MECP2 gene (PM1). The c.372G>T (p.Leu124Phe) variant in MECP2 is absent from gnomAD (PM2_supporting). The c.372G>C variant in the MECP2 gene results in a p.Leu124Phe change that is a previously established pathogenic variant (PMID 10991688, 12843318) (PS1). In summary, the c.372G>T (p.Leu124Phe) variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS1, PS2, PM1, PM2_supporting).
Met criteria codes
PS1
The c.372G>C variant in the MECP2 gene results in a p.Leu124Phe change that is a previously established pathogenic variant (PMID 10991688, 12843318) (PS1).
PS2
The p.Leu124Phe variant in MECP2 (NM_004992.3) occurs in the mosaic state in a male patient with a neurodevelopmental phenotype (internal database - Invitae) and therefore confirmed to be de novo (PS2).
PM1
The p.Leu124Phe variant occurs in the well-characterized methyl-DNA binding functional domain of the MECP2 gene (PM1).
PM2_Supporting
The p.Leu124Phe variant in MECP2 is absent from gnomAD (PM2_supporting).
Not Met criteria codes
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
REVEL score 0.61.
Curation History
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