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.379C>T (p.Arg127Cys)

CA294544

143541 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 3f058a05-d354-4c3c-ab58-d9f040ab9270

HGVS expressions

NM_001110792.2:c.379C>T

NM_001110792.2(MECP2):c.379C>T (p.Arg127Cys)

NC_000023.11:g.154032241G>A

CM000685.2:g.154032241G>A

NC_000023.10:g.153297692G>A

CM000685.1:g.153297692G>A

NC_000023.9:g.152950886G>A

NG_007107.2:g.109887C>T

NG_007107.3:g.109863C>T

ENST00000303391.11:c.343C>T

ENST00000453960.7:c.379C>T

ENST00000303391.10:c.343C>T

ENST00000369957.5:c.*397C>T

ENST00000407218.5:c.379C>T

ENST00000453960.6:c.379C>T

ENST00000486506.5:n.2691C>T

ENST00000611468.1:c.331C>T

ENST00000619732.4:c.343C>T

ENST00000622433.4:c.331C>T

ENST00000628176.2:c.343C>T

NM_001110792.1:c.379C>T

NM_001316337.1:c.64C>T

NM_004992.3:c.343C>T

NM_001316337.2:c.64C>T

NM_001369391.2:c.64C>T

NM_001369392.2:c.64C>T

NM_001369393.2:c.64C>T

NM_001369394.1:c.64C>T

NM_001369394.2:c.64C>T

NM_001386137.1:c.-218C>T

NM_001386138.1:c.-218C>T

NM_001386139.1:c.-218C>T

NM_004992.4:c.343C>T

Uncertain Significance

PP3 PM1 BS2 PM2_Supporting

PP4 PM6

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.Arg115Cys (NM_004992.4) in MECP2 occurs in the de novo state (biological parentage unconfirmed) in an individual with classic Rett syndrome; however, this individual was also heterozygous for a de novo truncating variant in MECP2 (PMID 18652533). The p.Arg115Cys variant (NM_004992.4) occurs in the well-characterized methyl-DNA binding (MDB) functional domain of MECP2 (PMID 21326358, 23770565) (PM1). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). The p.Arg115Cys variant (NM_004992.4) in MECP2 is absent from gnomAD (PM2_supporting). The p.Arg115Cys variant (NM_004992.4) is observed in at least 2 unaffected individuals (internal databases) (BS2). In summary, the p.Arg115Cys variant in MECP2 (NM_004992.4) is classified as a Variant of Uncertain Significance based on the ACMG/AMP criteria (PM1, PM2_supporting, PP3, BS2).

PP3

Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).

PM1

The p.Arg115Cys variant occurs in the well-characterized methyl-DNA binding (MDB) functional domain of MECP2 (PMID 21326358, 23770565) (PM1).

BS2

The p.Arg115Cys variant (NM_004992.4) is observed in at least 2 unaffected individuals (internal databases) (BS2).

PM2_Supporting

The p.Arg127Cys variant in MECP2 is absent from gnomAD (PM2_supporting).

PP4

The p.Arg115Cys variant in MECP2 has been identified in the hemizygous state in two males with seizures (internal database, GeneDx).

PM6

The p.Arg115Cys in MECP2 occurs in the de novo state (biological parentage unconfirmed) in an individual with classic Rett syndrome; however, this individual was also heterozygous for a de novo truncating variant in MECP2 (PMID 18652533).

Approved on: 2023-08-28

Published on: 2023-09-15

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