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.1018C>G (p.Leu340Val)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA270593

143756 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 11324803-9deb-4963-8788-8386d51c8983

Approved on: 2024-10-30

Published on: 2024-11-29

HGVS expressions

NM_001110792.2:c.1018C>G

NM_001110792.2(MECP2):c.1018C>G (p.Leu340Val)

NC_000023.11:g.154030846G>C

CM000685.2:g.154030846G>C

NC_000023.10:g.153296297G>C

CM000685.1:g.153296297G>C

NC_000023.9:g.152949491G>C

NG_007107.2:g.111282C>G

NG_007107.3:g.111258C>G

ENST00000303391.11:c.982C>G

ENST00000453960.7:c.1018C>G

ENST00000637917.1:c.156C>G

ENST00000303391.10:c.982C>G

ENST00000407218.5:c.*354C>G

ENST00000453960.6:c.1018C>G

ENST00000619732.4:c.982C>G

ENST00000622433.4:c.968C>G

ENST00000628176.2:c.*354C>G

NM_001110792.1:c.1018C>G

NM_001316337.1:c.703C>G

NM_004992.3:c.982C>G

NM_001316337.2:c.703C>G

NM_001369391.2:c.703C>G

NM_001369392.2:c.703C>G

NM_001369393.2:c.703C>G

NM_001369394.1:c.703C>G

NM_001369394.2:c.703C>G

NM_001386137.1:c.313C>G

NM_001386138.1:c.313C>G

NM_001386139.1:c.313C>G

NM_004992.4:c.982C>G

Likely Benign

BS2 BP5

PP3 PM1 BS1 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 p.Leu328Val variant in MECP2 (NM_004992.4) is observed in at least 2 unaffected individuals (internal database - Invitae) (BS2). The p.Leu328Val variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - Invitae; internal database - GeneDx) (BP5). The highest population minor allele frequency of the p.Leu328Val variant in MECP2 in gnomAD v4.1 is 0.00004283 in European (Finnish) population (not sufficient to meet BS1 criteria). In summary, the p.Leu328Val variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS2, BP5).

BS2

The p.Leu328Val variant is observed in at least 2 unaffected individuals (internal database - Invitae) (BS2).

BP5

The p.Leu328Val variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - Invitae; internal database - GeneDx) (BP5).

PP3

The computational predictor REVEL gives a score of 0.484 (PP3_not_met).

PM1

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

BS1

The highest population minor allele frequency of the p.Leu328Val variant in MECP2 (NM_004992.4) in gnomAD v4.1 is 0.00004283 in European (Finnish) population (not sufficient to meet BS1 criteria).

BP4

The computational predictor REVEL gives a score of 0.484 (BP4_not_met).

Curation History

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