Variant: NM_001110792.2(MECP2):c.1A>T (p.Met1Leu)

CA274666

156661 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

UUID: 8848c6dc-c0a0-47d8-9b94-3631b6b639b6

Approved on: 2024-10-30

Published on: 2024-12-20

HGVS expressions

NM_001110792.2:c.1A>T
NM_001110792.2(MECP2):c.1A>T (p.Met1Leu)
NC_000023.11:g.154097665T>A
CM000685.2:g.154097665T>A
NC_000023.10:g.153363122T>A
CM000685.1:g.153363122T>A
NC_000023.9:g.153016316T>A
NG_007107.2:g.44457A>T
NG_007107.3:g.44439A>T
ENST00000303391.11:c.-160A>T
ENST00000453960.7:c.1A>T
ENST00000303391.10:c.-160A>T
ENST00000407218.5:c.1A>T
ENST00000453960.6:c.1A>T
ENST00000619732.4:c.-160A>T
ENST00000627864.1:n.16A>T
ENST00000628176.2:c.-160A>T
ENST00000631210.1:n.305+7116A>T
NM_001110792.1:c.1A>T
NM_001316337.1:c.-607A>T
NM_004992.3:c.-160A>T
NM_001316337.2:c.-607A>T
NM_001369391.2:c.-902A>T
NM_001369392.2:c.-551A>T
NM_001369393.2:c.-427A>T
NM_001386137.1:c.-832A>T
NM_001386138.1:c.-720A>T
NM_001386139.1:c.-596A>T
NM_004992.4:c.-160A>T

Likely Pathogenic

• Met criteria codes: PP4 PS4_Moderate PM2_Supporting PM6_Strong

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MECP2 Version 3.0.0

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Met1Leu variant in MECP2 (NM_004992.4) has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with Rett syndrome (PMID: 16225173, GeneDx Internal Database) (PM6_strong, PP4). The p.Met1Leu variant has been observed in 4 individuals with clinical features of Rett syndrome (PMID: 16225173, 19365833, GeneDx Internal Database) (PS4_moderate). The p.Met1Leu variant in MECP2 is absent from gnomAD (PM2_supporting). In summary, the p.Met1Leu variant in MECP2 is classified as Likely Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PM6_strong, PS4_moderate, PP4, PM2_supporting).

Met criteria codes

• PP4: The p.Met1Leu variant in MECP2 (NM_004992.4) has been reported in an individual with a clinical phenotype suggestive of Rett syndrome (PMID: 16225173) (PP4_met).
• PS4_Moderate: The p.Met1Leu variant has been observed in 4 individuals with clinical features of Rett syndrome (PMID: 16225173, 19365833, GeneDx Internal Database) (PS4_moderate).
• PM2_Supporting: The p.Met1Leu variant in MECP2 (NM_004992.4) is absent from gnomAD (PM2_supporting).
• PM6_Strong: The p.Met1Leu variant in MECP2 (NM_004992.4) has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with Rett syndrome (PMID: 16225173, GeneDx Internal Database) (PM6_strong).