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.1117C>G (p.Pro373Ala)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA170169

143325 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 7cbfcbcb-7004-4b7d-950b-0913785b1292

Approved on: 2025-06-25

Published on: 2025-08-01

HGVS expressions

NM_001110792.2:c.1117C>G

NM_001110792.2(MECP2):c.1117C>G (p.Pro373Ala)

NC_000023.11:g.154030747G>C

CM000685.2:g.154030747G>C

NC_000023.10:g.153296198G>C

CM000685.1:g.153296198G>C

NC_000023.9:g.152949392G>C

NG_007107.2:g.111381C>G

NG_007107.3:g.111357C>G

ENST00000303391.11:c.1081C>G

ENST00000453960.7:c.1117C>G

ENST00000303391.10:c.1081C>G

ENST00000407218.5:c.*453C>G

ENST00000453960.6:c.1117C>G

ENST00000619732.4:c.1081C>G

ENST00000628176.2:c.*453C>G

NM_001110792.1:c.1117C>G

NM_001316337.1:c.802C>G

NM_004992.3:c.1081C>G

NM_001316337.2:c.802C>G

NM_001369391.2:c.802C>G

NM_001369392.2:c.802C>G

NM_001369393.2:c.802C>G

NM_001369394.1:c.802C>G

NM_001369394.2:c.802C>G

NM_001386137.1:c.412C>G

NM_001386138.1:c.412C>G

NM_001386139.1:c.412C>G

NM_004992.4:c.1081C>G

Benign

BS2 BS1 BP5

BA1 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 4.1.0

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.Pro361Ala variant in MECP2 (NM_004992.4) in gnomAD v4.1 is 0.0001029 in the Non-Finnish European population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.00008) for BS1, and therefore meets this criterion (BS1). The p.Pro361Ala variant is observed in at least 2 unaffected individuals (Internal database - Ambry Genetics) (BS2). The p.Pro361Ala variant is found in a patient with an alternate molecular basis of disease (internal database - Labcorp Genetics) (BP5). In summary, the p.Pro361Ala variant in MECP2 (NM_004992.4) is classified as benign based on ACMG/AMP criteria (BS1, BS2, BP5). (MECP2 Specifications v.4.1; curation approved on 06/25/2025)

BS2

The p.Pro361Ala variant in MECP2 (NM_004992.4) is observed in at least 2 unaffected individuals (Internal database - Ambry Genetics) (BS2).

BS1

BP5

The p.Pro361Ala variant in MECP2 (NM_004992.4) is found in a patient with an alternate molecular basis of disease (internal database - Labcorp Genetics) (BP5).

BA1

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

BP4

Computational prediction analysis tools are inconclusive for this variant.

Curation History

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