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.1000C>T (p.Pro334Ser)

CA121715

11843 (ClinVar)

Gene: MECP2 (HGNC:4204)

Condition: Rett syndrome (MONDO:0010726)

Inheritance Mode: X-linked inheritance

UUID: b1a3e12a-4186-4ed2-9306-7f7f50d8f2ee

Approved on: 2026-07-01

Published on: 2026-09-30

HGVS expressions

NM_001110792.2:c.1000C>T

NM_001110792.2(MECP2):c.1000C>T (p.Pro334Ser)

NC_000023.11:g.154030864G>A

CM000685.2:g.154030864G>A

NC_000023.10:g.153296315G>A

CM000685.1:g.153296315G>A

NC_000023.9:g.152949509G>A

NG_007107.2:g.111264C>T

NG_007107.3:g.111240C>T

ENST00000303391.11:c.964C>T

ENST00000453960.7:c.1000C>T

ENST00000637917.1:c.138C>T

ENST00000303391.10:c.964C>T

ENST00000407218.5:c.*336C>T

ENST00000453960.6:c.1000C>T

ENST00000619732.4:c.964C>T

ENST00000622433.4:c.950C>T

ENST00000628176.2:c.*336C>T

NM_001110792.1:c.1000C>T

NM_001316337.1:c.685C>T

NM_004992.3:c.964C>T

NM_001316337.2:c.685C>T

NM_001369391.2:c.685C>T

NM_001369392.2:c.685C>T

NM_001369393.2:c.685C>T

NM_001369394.1:c.685C>T

NM_001369394.2:c.685C>T

NM_001386137.1:c.295C>T

NM_001386138.1:c.295C>T

NM_001386139.1:c.295C>T

NM_004992.4:c.964C>T

Pathogenic

PS4 PS2_Very Strong PM2_Supporting

PP3 BP4

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 6.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Pro322Ser variant in MECP2 (NM_004992.3) has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in 4 individuals with features of Rett syndrome (CeGaT Center for Human Genetics Tuebingen, GeneDx, Equipe Genetique des Anomalies du Developpement (Université de Bourgogne), GADteam, and Labcorp Genetics (formerly Invitae) internal databases) (PS2_Very Strong). The p.Pro322Ser variant has been observed in at least 5 individuals with features of Rett syndrome (PMIDs: 38540345, 16966553, 30573328, 30536762, CeGaT Center for Human Genetics Tuebingen and GeneDx internal databases) (PS4). The p.Pro322Ser variant in MECP2 is absent from gnomAD v4 (PM2_Supporting). In summary, the p.Pro322Ser variant in MECP2 is classified as pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS2_Very Strong, PS4, PM2_Supporting). (MECP2 Specifications v6.0.0; curation approved on 7/1/2026.)

PS4

The p.Pro322Ser variant has been observed in at least 5 individuals with features of Rett syndrome (PMID 38540345, 16966553, 30573328, 30536762, CeGaT Center for Human Genetics Tuebingen and GeneDx internal databases) (PS4).

PS2_Very Strong

The p.Pro322Ser variant in MECP2 has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in 4 individuals with features of Rett syndrome (CeGaT Center for Human Genetics Tuebingen, GeneDx, Equipe Genetique des Anomalies du Developpement (Université de Bourgogne), GADteam, and Labcorp Genetics (formerly Invitae) internal databases) (PS2_Very Strong).

PM2_Supporting

The p.Pro322Ser variant in MECP2 is absent from gnomAD v4 (PM2_Supporting).

PP3

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

BP4

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

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.