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.1028A>G (p.Lys343Arg)

CA170424

143761 (ClinVar)

Gene: MECP2 (HGNC:4204)

Condition: Rett syndrome (MONDO:0010726)

Inheritance Mode: X-linked inheritance

UUID: a23b2266-fd96-489c-b4b3-f179ad337a3d

Approved on: 2025-02-28

Published on: 2025-03-26

HGVS expressions

NM_001110792.2:c.1028A>G

NM_001110792.2(MECP2):c.1028A>G (p.Lys343Arg)

NC_000023.11:g.154030836T>C

CM000685.2:g.154030836T>C

NC_000023.10:g.153296287T>C

CM000685.1:g.153296287T>C

NC_000023.9:g.152949481T>C

NG_007107.2:g.111292A>G

NG_007107.3:g.111268A>G

ENST00000303391.11:c.992A>G

ENST00000453960.7:c.1028A>G

ENST00000303391.10:c.992A>G

ENST00000407218.5:c.*364A>G

ENST00000453960.6:c.1028A>G

ENST00000619732.4:c.992A>G

ENST00000628176.2:c.*364A>G

NM_001110792.1:c.1028A>G

NM_001316337.1:c.713A>G

NM_004992.3:c.992A>G

NM_001316337.2:c.713A>G

NM_001369391.2:c.713A>G

NM_001369392.2:c.713A>G

NM_001369393.2:c.713A>G

NM_001369394.1:c.713A>G

NM_001369394.2:c.713A>G

NM_001386137.1:c.323A>G

NM_001386138.1:c.323A>G

NM_001386139.1:c.323A>G

NM_004992.4:c.992A>G

Uncertain Significance

PM2_Supporting PP4 BS2_Supporting

PP3 PM1 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 3.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The NM_004992.4:c.992A>G (p.Lys331Arg) variant in MECP2 has been reported in an individual with a clinical phenotype suggestive of Rett syndrome (PMID: 21212452) (PP4) and in at least 1 unaffected individual (PMID: 21212452) (BS2_Supporting). The p.Lys331Arg variant in MECP2 is absent from gnomAD v4.1 (PM2_Supporting). Computational prediction analysis tools are inconclusive for this variant (REVEL gives a score of 0.459). Due to conflicting evidence, this variant is classified as a variant of uncertain significance for Rett syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Rett and Angelman-like disorders VCEP (BS2_Supporting, PM2_Supporting, PP4) (MECP2 Specifications v3.0; curation approved on 2/28/2025).

PM2_Supporting

The p.Lys331Arg variant in MECP2 (NM_004992.4) is absent from gnomAD v4.1 (PM2_Supporting).

PP4

The p.Lys331Arg variant in MECP2 (NM_004992.4) has been reported in an individual with a clinical phenotype suggestive of Rett syndrome (PMID: 21212452) (PP4).

BS2_Supporting

The p.Lys331Arg variant (NM_004992.4) is observed in at least 1 unaffected individual (PMID: 21212452) (BS2_Supporting).

PP3

Computational prediction analysis tools are inconclusive for this variant (REVEL gives a score of 0.459).

PM1

outside PM1 region

BP4

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

Curation History

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