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)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA170424

143761 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

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 BS2_Supporting PP4

BP4 PP3 PM1

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).

BS2_Supporting

The p.Lys331Arg variant (NM_004992.4) is observed in at least 1 unaffected individual (PMID: 21212452) (BS2_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).

BP4

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

PP3

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

PM1

outside PM1 region

Curation History

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