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_001110792.2(MECP2):c.338C>G (p.Pro113Arg)

CA274626

143526 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: f3b3ee49-05e1-4b1b-9eac-caaee4fc5588

HGVS expressions

NM_001110792.2:c.338C>G

NM_001110792.2(MECP2):c.338C>G (p.Pro113Arg)

NC_000023.11:g.154032282G>C

CM000685.2:g.154032282G>C

NC_000023.10:g.153297733G>C

CM000685.1:g.153297733G>C

NC_000023.9:g.152950927G>C

NG_007107.2:g.109846C>G

NG_007107.3:g.109822C>G

ENST00000303391.11:c.302C>G

ENST00000453960.7:c.338C>G

ENST00000303391.10:c.302C>G

ENST00000369957.5:c.*356C>G

ENST00000407218.5:c.338C>G

ENST00000453960.6:c.338C>G

ENST00000486506.5:n.2650C>G

ENST00000611468.1:c.290C>G

ENST00000619732.4:c.302C>G

ENST00000622433.4:c.290C>G

ENST00000628176.2:c.302C>G

NM_001110792.1:c.338C>G

NM_001316337.1:c.23C>G

NM_004992.3:c.302C>G

NM_001316337.2:c.23C>G

NM_001369391.2:c.23C>G

NM_001369392.2:c.23C>G

NM_001369393.2:c.23C>G

NM_001369394.1:c.23C>G

NM_001369394.2:c.23C>G

NM_001386137.1:c.-259C>G

NM_001386138.1:c.-259C>G

NM_001386139.1:c.-259C>G

NM_004992.4:c.302C>G

Pathogenic

PS4 PP3 PM5_Strong PM2_Supporting

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.Pro101Arg variant in MECP2 (NM_004992.4) has been observed in 4 other individuals with Rett Syndrome (PMID 10991689, RettBASE proband ID: 4426, 6597, 6598) and another individual with Angelman syndrome-like phenotype (PMID 11283202) (PS4). Multiple pathogenic missense variants (p.Pro101His, p.Pro101Leu, p.Pro101Thr, p.Pro101Ser) have been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 11269512, RettBASE)(PM5_Strong). The p.Pro101Arg variant in MECP2 is absent from gnomAD (PM2_supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary the p.Pro101Arg variant in MECP2 is classified as Pathogenic for Rett Syndrome based on the ACMG/AMP criteria (PS4, PM5_Strong, PM2_supporting, PP3).

PS4

PS4: The p.Pro101Arg variant has been observed in 4 other individuals with Rett Syndrome (PMID 10991689,RettBASE proband id 4426,6597,6598) and another individual with Angelman syndrome-like phenotype(PMID 11283202)

PP3

Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own

PM5_Strong

Multiple pathogenic missense variants p.Pro101His,p.Pro101Leu have been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 11269512, RettBASE )(PM5_Strong)

PM2_Supporting

The p.Pro101Arg variant in MECP2 is absent from gnomAD

Approved on: 2022-04-28

Published on: 2023-01-04

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