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.1497A>G (p.Ter499Trp)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA170257

143490 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 2bba9172-4eb1-4098-97c0-63efb3d2ff5b

Approved on: 2025-10-28

Published on: 2025-12-23

HGVS expressions

NM_001110792.2:c.1497A>G

NM_001110792.2(MECP2):c.1497A>G (p.Ter499Trp)

NC_000023.11:g.154030367T>C

CM000685.2:g.154030367T>C

NC_000023.10:g.153295818T>C

CM000685.1:g.153295818T>C

NC_000023.9:g.152949012T>C

NG_007107.2:g.111761A>G

NG_007107.3:g.111737A>G

ENST00000303391.11:c.1461A>G

ENST00000453960.7:c.1497A>G

ENST00000303391.10:c.1461A>G

ENST00000453960.6:c.1497A>G

ENST00000619732.4:c.1457A>G

ENST00000628176.2:c.*833A>G

NM_001110792.1:c.1497A>G

NM_001316337.1:c.1182A>G

NM_004992.3:c.1461A>G

NM_001316337.2:c.1182A>G

NM_001369391.2:c.1182A>G

NM_001369392.2:c.1182A>G

NM_001369393.2:c.1182A>G

NM_001369394.1:c.1182A>G

NM_001369394.2:c.1182A>G

NM_001386137.1:c.792A>G

NM_001386138.1:c.792A>G

NM_001386139.1:c.792A>G

NM_004992.4:c.1461A>G

Pathogenic

PM4_Strong PS4_Moderate PS2 PM2_Supporting

PP4

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MECP2 Version 5.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Ter487TrpextTer27 variant in MECP2 (NM_004992.4) occurs at the stop codon and causes a change in the length of the protein and an elongated mRNA transcript of MECP2 (PM4_strong). The p.Ter487TrpextTer27 variant in MECP2 has been reported as a de novo occurrence (biological parentage confirmed) in an individual with features of Rett syndrome (internal database - GeneDx) (PS2). The p.Ter487TrpextTer27 variant has been observed in 3 individuals with features of Rett syndrome (PMID 21807996; internal database - LabCorp (formerly Invitae); internal database - GeneDx) (PS4_moderate). The p.Ter487TrpextTer27 variant in MECP2 is absent from gnomAD v4.1.0 (PM2_supporting). In summary, the p.Ter487TrpextTer27 variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PM4_strong, PS2, PS4_moderate, PM2_supporting). (MECP2 Specifications v5.0.0; curation approved on 10/28/2025).

PM4_Strong

The p.Ter487TrpextTer27 variant in MECP2 (NM_004992.4) occurs at the stop codon and causes a change in the length of the protein and an elongated mRNA transcript of MECP2 (PM4_strong).

PS4_Moderate

The p.Ter487TrpextTer27 variant has been observed in 3 individuals with features of Rett syndrome (PMID 21807996; internal database - LabCorp (formerly Invitae); internal database - GeneDx) (PS4_moderate).

PS2

The p.Ter487TrpextTer27 variant in MECP2 (NM_004992.4) has been reported as a de novo occurrence (biological parentage confirmed) in an individual with a neurodevelopmental disorder (internal database - GeneDx) (PS2).

PM2_Supporting

The p.Ter487TrpextTer27 variant in MECP2 is absent from gnomAD (PM2_supporting).

PP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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