Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001110792.2(MECP2):c.1286A>T (p.Lys429Met)

CA280048

143450 (ClinVar)

Gene: MECP2
Condition: Rett syndrome
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: fa614af7-6e48-4d68-90b0-b12eb5475336
Approved on: 2025-10-28
Published on: 2025-12-23

HGVS expressions

NM_001110792.2:c.1286A>T
NM_001110792.2(MECP2):c.1286A>T (p.Lys429Met)
NC_000023.11:g.154030578T>A
CM000685.2:g.154030578T>A
NC_000023.10:g.153296029T>A
CM000685.1:g.153296029T>A
NC_000023.9:g.152949223T>A
NG_007107.2:g.111550A>T
NG_007107.3:g.111526A>T
ENST00000303391.11:c.1250A>T
ENST00000453960.7:c.1286A>T
ENST00000303391.10:c.1250A>T
ENST00000453960.6:c.1286A>T
ENST00000619732.4:c.1250A>T
ENST00000628176.2:c.*622A>T
NM_001110792.1:c.1286A>T
NM_001316337.1:c.971A>T
NM_004992.3:c.1250A>T
NM_001316337.2:c.971A>T
NM_001369391.2:c.971A>T
NM_001369392.2:c.971A>T
NM_001369393.2:c.971A>T
NM_001369394.1:c.971A>T
NM_001369394.2:c.971A>T
NM_001386137.1:c.581A>T
NM_001386138.1:c.581A>T
NM_001386139.1:c.581A>T
NM_004992.4:c.1250A>T
More

Benign

Met criteria codes 2
BS2 BS1
Not Met criteria codes 5
BP4 PP3 PP4 PM1 PM2

Evidence Links 0

Expert Panel

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 highest population minor allele frequency of the p.Lys417Met variant in MECP2 (NM_004992.4) in gnomAD v4.1.0 is 0.00001764 in the African/African American population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.0000083) for BS1, and therefore meets this criterion (BS1). The p.Lys417Met variant in MECP2 is observed in at least 2 unaffected individuals (PMID 16832102; internal database - GeneDx; internal database - Ambry) (BS2). The p.Lys417Met variant in MECP2 has been reported in a male with early onset encephalopathy (PMID 16832102) (no criteria met). In summary, the p.Lys417Met variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BS1, BS2). (MECP2 Specifications v5.0.0; curation approved on 10/28/2025)
Met criteria codes
BS2
The p.Lys417Met variant in MECP2 is observed in at least 2 unaffected individuals (PMID 16832102; internal database - GeneDx; internal database - Ambry) (BS2).
BS1
The highest population minor allele frequency of the p.Lys417Met variant in MECP2 (NM_004992.4) in gnomAD v4.1.0 is 0.00001764 in the African/African American population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.0000083) for BS1, and therefore meets this criterion (BS1).
Not Met criteria codes
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
REVEL 0.416
PP4
The p.Lys417Met variant in MECP2 has been reported in an individual with early onset encephalopathy (PMID 16832102) (PP4 not met).
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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