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.334C>G (p.Leu112Val)

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

PM2_Supporting PS4 PP3 PM6 PM1

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).

PM2_Supporting

The p.Leu100Val variant in MECP2 is absent from gnomAD

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

PM6

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

PM1

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

BP4

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

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