Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • See Evidence submitted by expert panel for details.

Variant: NM_001110792.2(MECP2):c.400G>A (p.Val134Met)

CA270366

143546 (ClinVar)

Gene: MECP2
Condition: Rett syndrome
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 524c0c15-0c45-4f53-a9b3-ab6d2536879f
Approved on: 2021-10-26
Published on: 2021-12-27

HGVS expressions

NM_001110792.2:c.400G>A
NM_001110792.2(MECP2):c.400G>A (p.Val134Met)
NC_000023.11:g.154032220C>T
CM000685.2:g.154032220C>T
NC_000023.10:g.153297671C>T
CM000685.1:g.153297671C>T
NC_000023.9:g.152950865C>T
NG_007107.2:g.109908G>A
NG_007107.3:g.109884G>A
ENST00000303391.11:c.364G>A
ENST00000453960.7:c.400G>A
ENST00000303391.10:c.364G>A
ENST00000369957.5:c.*418G>A
ENST00000407218.5:c.400G>A
ENST00000453960.6:c.400G>A
ENST00000486506.5:n.2712G>A
ENST00000611468.1:c.352G>A
ENST00000619732.4:c.364G>A
ENST00000622433.4:c.352G>A
ENST00000628176.2:c.364G>A
NM_001110792.1:c.400G>A
NM_001316337.1:c.85G>A
NM_004992.3:c.364G>A
NM_001316337.2:c.85G>A
NM_001369391.2:c.85G>A
NM_001369392.2:c.85G>A
NM_001369393.2:c.85G>A
NM_001369394.1:c.85G>A
NM_001369394.2:c.85G>A
NM_001386137.1:c.-197G>A
NM_001386138.1:c.-197G>A
NM_001386139.1:c.-197G>A
NM_004992.4:c.364G>A
More

Pathogenic

Met criteria codes 6
PM2_Supporting PS2 PS4_Supporting PP4 PP3 PM1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Val122Met variant in MECP2 (NM_004992.3) has been reported in an individual with a clinical phenotype suggestive of Rett syndrome (PMID: 17089071) (PP4). The p.Val122Met variant in MECP2 occurs in the de novo state (biological parentage unconfirmed) in this individual. It is also reported in the mosaic state in a male patient with clinical features of Rett syndrome (PMID 28837158, internal database - GeneDx) and therefore confirmed to be de novo (PS2, PS4_supporting). The p.Val122Met variant occurs in the well-characterized methyl-DNA binding (MDB) functional domain of MECP2 (PM1). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). The p.Val122Met variant in MECP2 is absent from gnomAD (PM2_supporting). In summary, the p.Val122Met variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS2, PM1, PS4_supporting, PM2_supporting, PP3, PP4).
Met criteria codes
PM2_Supporting
The p.Val122Met variant in MECP2 is absent from gnomAD (PM2_supporting).
PS2
The p.Val122Met variant in MECP2 occurs in the de novo state (biological parentage unconfirmed) in this individual. It is also reported in the mosaic state in a male patient with clinical features of Rett syndrome (PMID 28837158, internal database - GeneDx) and therefore confirmed to be de novo (PS2).
PS4_Supporting
The p.Val122Met variant has been observed in at least 1 other individual with clinical features of Rett syndrome (PMID 28837158) (PS4_supporting).
PP4
The p.Val122Me variant in MECP2 has been reported in an individual with a clinical phenotype suggestive of Rett syndrome (PMID: 17089071) (PP4).
PP3
Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).
PM1
The p.Val122Met variant occurs in the well-characterized methyl-DNA binding (MDB) functional domain of MECP2 (PM1).
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.