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.1097G>T (p.Arg366Leu)

CA170157

143317 (ClinVar)

Gene: MECP2 (HGNC:4204)

Condition: Rett syndrome (MONDO:0010726)

Inheritance Mode: X-linked inheritance

UUID: 36c5a87e-0e4c-45fe-a7b8-8c1788eef672

Approved on: 2025-05-07

Published on: 2025-06-30

HGVS expressions

NM_001110792.2(MECP2):c.1097G>T (p.Arg366Leu)

NM_001110792.2:c.1097G>T

NC_000023.11:g.154030767C>A

CM000685.2:g.154030767C>A

NC_000023.10:g.153296218C>A

CM000685.1:g.153296218C>A

NC_000023.9:g.152949412C>A

NG_007107.2:g.111361G>T

NG_007107.3:g.111337G>T

ENST00000303391.11:c.1061G>T

ENST00000453960.7:c.1097G>T

ENST00000303391.10:c.1061G>T

ENST00000407218.5:c.*433G>T

ENST00000453960.6:c.1097G>T

ENST00000619732.4:c.1061G>T

ENST00000628176.2:c.*433G>T

NM_001110792.1:c.1097G>T

NM_001316337.1:c.782G>T

NM_004992.3:c.1061G>T

NM_001316337.2:c.782G>T

NM_001369391.2:c.782G>T

NM_001369392.2:c.782G>T

NM_001369393.2:c.782G>T

NM_001369394.1:c.782G>T

NM_001369394.2:c.782G>T

NM_001386137.1:c.392G>T

NM_001386138.1:c.392G>T

NM_001386139.1:c.392G>T

NM_004992.4:c.1061G>T

Benign

BS2 BS1

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 4.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Arg354Leu variant in MECP2 (NM_004992.4) is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). The highest population minor allele frequency of the p.Arg354Leu variant in MECP2 in gnomAD v4.1 is 0.0001252 in the European (non-Finnish) population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.00008) for BS1 and therefore meets this criterion (BS1). In summary, the p.Arg354Leu variant in MECP2 is classified as benign based on the ACMG/AMP criteria (BS1, BS2). (MECP2 Specifications v.4.1; curation approved on [5/7/2025])

BS2

The p.Arg354Leu variant in MECP2 (NM_004992.4) is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2).

BS1

The highest population minor allele frequency of the p.Arg354Leu variant in MECP2 (NM_004992.4) in gnomAD v4.1 is 0.0001252 in the European (non-Finnish) population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.00008) for BS1, and therefore meets this criterion (BS1).

Curation History

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