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.334C>G (p.Leu112Val)

Curation Version - 1.0
Curation History
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CA198822

11835 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: e3bdc1b4-4132-4891-9922-81a05eb5f882

Approved on: 2022-05-10

Published on: 2022-06-28

HGVS expressions

NM_001110792.2:c.334C>G

NM_001110792.2(MECP2):c.334C>G (p.Leu112Val)

NC_000023.11:g.154032286G>C

CM000685.2:g.154032286G>C

NC_000023.10:g.153297737G>C

CM000685.1:g.153297737G>C

NC_000023.9:g.152950931G>C

NG_007107.2:g.109842C>G

NG_007107.3:g.109818C>G

ENST00000303391.11:c.298C>G

ENST00000453960.7:c.334C>G

ENST00000303391.10:c.298C>G

ENST00000369957.5:c.*352C>G

ENST00000407218.5:c.334C>G

ENST00000453960.6:c.334C>G

ENST00000486506.5:n.2646C>G

ENST00000611468.1:c.286C>G

ENST00000619732.4:c.298C>G

ENST00000622433.4:c.286C>G

ENST00000628176.2:c.298C>G

NM_001110792.1:c.334C>G

NM_001316337.1:c.19C>G

NM_004992.3:c.298C>G

NM_001316337.2:c.19C>G

NM_001369391.2:c.19C>G

NM_001369392.2:c.19C>G

NM_001369393.2:c.19C>G

NM_001369394.1:c.19C>G

NM_001369394.2:c.19C>G

NM_001386137.1:c.-263C>G

NM_001386138.1:c.-263C>G

NM_001386139.1:c.-263C>G

NM_004992.4:c.298C>G

Pathogenic

PM1 PM6 PS4 PP3 PM2_Supporting

BP4

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.Leu100Val (NM_004992) variant has been observed in at least 5 other individuals with Rett Syndrome (PMID: 22476991, 16672765, 12966522, 11913567, 11055898, RettBASE) (PS4). The p.Leu100Val variant occurs in the well-characterized Methyl-DNA binding [MBD] functional domain of the MECP2 (PM1). The p.Leu100Val variant in MECP2 is absent from gnomAD (PM2_supporting). The p.Leu100Val variant in MECP2 occurs in the de novo state (biological parentage unconfirmed) in an individual with mild atypical Rett syndrome (PMID: 12966522)(PM6). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Leu100Val variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS4, PM1, PM6, PM2_supporting, PP3).

PM1

The p.Leu100Val variant occurs in the well-characterized Methyl-DNA binding [MBD] functional domain of the MECP2

PM6

The p.Leu100Val variant in MECP2 occurs in the de novo state (biological parentage unconfirmed) in this individual (PMID:12966522)

PS4

The p.Leu100Val variant has been observed in at least 5 other individuals with Rett Syndrome (PMID: 22476991, 16672765,12966522,11913567,11055898, RettBASE)

PP3

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

PM2_Supporting

The p.Leu100Val variant in MECP2 is absent from gnomAD

BP4

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

Curation History

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