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]

Link to SEPIO compliant JSON-LD document

Variant: NM_004992.3:c.295A>C

CA415176953

859603 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 53cbe232-7c99-4325-bff3-5a5ee6b4f5ec

HGVS expressions

NM_004992.3:c.295A>C

ENST00000303391.11:c.295A>C

ENST00000453960.7:c.331A>C

ENST00000303391.10:c.295A>C

ENST00000369957.5:c.*349A>C

ENST00000407218.5:c.331A>C

ENST00000453960.6:c.331A>C

ENST00000486506.5:n.2643A>C

ENST00000611468.1:c.283A>C

ENST00000619732.4:c.295A>C

ENST00000622433.4:c.283A>C

ENST00000628176.2:c.295A>C

NM_001110792.1:c.331A>C

NM_001316337.1:c.16A>C

NM_001110792.2:c.331A>C

NM_001316337.2:c.16A>C

NM_001369391.2:c.16A>C

NM_001369392.2:c.16A>C

NM_001369393.2:c.16A>C

NM_001369394.1:c.16A>C

NM_001369394.2:c.16A>C

NM_001386137.1:c.-266A>C

NM_001386138.1:c.-266A>C

NM_001386139.1:c.-266A>C

NM_004992.4:c.295A>C

NC_000023.11:g.154032289T>G

CM000685.2:g.154032289T>G

NC_000023.10:g.153297740T>G

CM000685.1:g.153297740T>G

NC_000023.9:g.152950934T>G

NG_007107.2:g.109839A>C

NG_007107.3:g.109815A>C

Uncertain Significance

PM2_Supporting PP4 PM1

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Thr99Pro variant in MECP2 occurs in the well-characterized methyl-DNA binding (MDB) functional domain of the MECP2 gene (PMID 21326358) (PM1). This variant has been reported in an individual with a clinical phenotype suggestive of Rett Syndrome (internal database) (PP4). The p.Thr99Pro variant is absent from gnomAD (PM2_supporting). In summary, the p.Thr99Pro variant in MECP2 is classified as a Variant of Uncertain Significance based on the ACMG/AMP criteria (PM1, PM2_supporting, PP4).

PM2_Supporting

The variant p.Thr99Pro in MECP2 gene is absent from gnomAD (PM2_supporting).

PP4

The patient is reported to have a clinical phenotype suggestive of atypical Rett Syndrome

PM1

The variant p.Thr99Pro in MECP2 is affecting a mutational hotspot (Methyl-DNA binding (MDB) domain affecting between aa 90-162; (PMID 21326358) PM1

Approved on: 2021-03-26

Published on: 2021-05-17

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