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]
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Variant: NM_004992.3(MECP2):c.301C>T (p.Pro101Ser)

CA270328

143524 (ClinVar)

Gene: MECP2
Condition: Rett syndrome
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 2b8ace0a-d687-49ca-a70c-e5ca323bc4b3

HGVS expressions

NM_004992.3:c.301C>T
NM_004992.3(MECP2):c.301C>T (p.Pro101Ser)
ENST00000303391.11:c.301C>T
ENST00000453960.7:c.337C>T
ENST00000303391.10:c.301C>T
ENST00000369957.5:c.*355C>T
ENST00000407218.5:c.337C>T
ENST00000453960.6:c.337C>T
ENST00000486506.5:n.2649C>T
ENST00000611468.1:c.289C>T
ENST00000619732.4:c.301C>T
ENST00000622433.4:c.289C>T
ENST00000628176.2:c.301C>T
NM_001110792.1:c.337C>T
NM_001316337.1:c.22C>T
NM_001110792.2:c.337C>T
NM_001316337.2:c.22C>T
NM_001369391.2:c.22C>T
NM_001369392.2:c.22C>T
NM_001369393.2:c.22C>T
NM_001369394.1:c.22C>T
NM_001369394.2:c.22C>T
NM_001386137.1:c.-260C>T
NM_001386138.1:c.-260C>T
NM_001386139.1:c.-260C>T
NM_004992.4:c.301C>T
NC_000023.11:g.154032283G>A
CM000685.2:g.154032283G>A
NC_000023.10:g.153297734G>A
CM000685.1:g.153297734G>A
NC_000023.9:g.152950928G>A
NG_007107.2:g.109845C>T
NG_007107.3:g.109821C>T

Pathogenic

Met criteria codes 6
PM5_Strong PS4 PM2_Supporting PP3 PP4 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.Pro101Ser variant has been observed in at least 4 other individuals with Rett syndrome (RettBASE, internal database) (PS4). Multiple pathogenic missense variants have been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 10767337, 31439979) (PM5_Strong). The p.Pro101Ser variant in MECP2 is absent from gnomAD (PM2_Supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). The p.Pro101Ser variant in MECP2 has been reported in an individual with a clinical phenotype suggestive of Rett syndrome (PMID 11269512) (PP4). In summary, the p.Pro101Ser variant in MECP2 is classified as pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS4, PM5_strong, PM2_supporting, PP3, PP4).
Met criteria codes
PM5_Strong
Multiple pathogenic missense variants have been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 10767337, 31439979)
PS4
The p.Pro101Ser variant has been observed in at least 4 other individuals with Rett syndrome (RettBASE, internal database)
PM2_Supporting
The p.Pro101Ser variant in MECP2 is absent from gnomAD
PP3
Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own
PP4
The p.Pro101Ser variant in MECP2 has been reported in an individual with a clinical phenotype suggestive of Rett syndrome (PMID 11269512)
PM1
The variant p.Pro101Ser in MECP2 is affecting a mutational hotspot (Methyl-DNA binding (MDB) domain: between aa 90-162; PM1
Approved on: 2021-03-26
Published on: 2021-05-17
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