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.433C>T (p.Arg145Cys)

CA211250

11809 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 9b84fa8c-1789-41fa-a192-056f88af3907

HGVS expressions

NM_001110792.2:c.433C>T

NM_001110792.2(MECP2):c.433C>T (p.Arg145Cys)

NC_000023.11:g.154031431G>A

CM000685.2:g.154031431G>A

NC_000023.10:g.153296882G>A

CM000685.1:g.153296882G>A

NC_000023.9:g.152950076G>A

NG_007107.2:g.110697C>T

NG_007107.3:g.110673C>T

ENST00000303391.11:c.397C>T

ENST00000453960.7:c.433C>T

ENST00000637917.1:n.30C>T

ENST00000303391.10:c.397C>T

ENST00000369957.5:c.*451C>T

ENST00000407218.5:c.433C>T

ENST00000453960.6:c.433C>T

ENST00000486506.5:n.2745C>T

ENST00000611468.1:c.385C>T

ENST00000619732.4:c.397C>T

ENST00000622433.4:c.385C>T

ENST00000628176.2:c.397C>T

NM_001110792.1:c.433C>T

NM_001316337.1:c.118C>T

NM_004992.3:c.397C>T

NM_001316337.2:c.118C>T

NM_001369391.2:c.118C>T

NM_001369392.2:c.118C>T

NM_001369393.2:c.118C>T

NM_001369394.1:c.118C>T

NM_001369394.2:c.118C>T

NM_001386137.1:c.-164C>T

NM_001386138.1:c.-164C>T

NM_001386139.1:c.-164C>T

NM_004992.4:c.397C>T

Pathogenic

PM1 PM2_Supporting PS2_Very Strong PS4 PP3

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.Arg133Cys (NM_004992) variant in MECP2 has been reported as an assumed de novo occurrence in at least 4 individuals with Rett Syndrome (PMID: 10814718, PMID: 10991688, PMID: 12707946) (PS2_very-strong). The p.Arg133Cys variant has been observed in at least 4 other individuals with Rett Syndrome (PMID: 10814718, PMID: 10991688, PMID: 12707946, PMID: 17387578, PMID: 16473305) (PS4). The p.Arg133Cys variant occurs in the well-characterized (Methyl-DNA binding [MDB]: aa 90-162) functional domain of the MECP2 (PM1). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). The p.Arg133Cys variant in MECP2 is absent from gnomAD (PM2_Supporting). In summary the p.Arg133Cys variant in MECP2 is classified as Pathogenic for Rett Syndrome based on the ACMG/AMP criteria (PS2_very-strong, PS4, PM1, PP3, PM2_supporting).

PM1

The p.Arg133Cys variant occurs in the well-characterized (Methyl-DNA binding [MDB]: aa 90-162; ) functional domain of the MECP2

PM2_Supporting

The p.Arg133Cys variant in MECP2 is absent from gnomAD

PS2_Very Strong

The p.Arg133Cys variant in MECP2 has been reported as an assumed de novo occurrence in at least 4 individuals with Rett Syndrome(PMID: 10814718,PMID: 10991688,PMID: 12707946)

PS4

The p.Arg133Cys variant has been observed in at least 4 other individuals with Rett Syndrome(PMID: 10814718,PMID: 10991688,PMID: 12707946,PMID:17387578,PMID:16473305)

PP3

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

Approved on: 2022-05-10

Published on: 2022-07-25

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