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.1001C>T (p.Pro334Leu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA270591

143754 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 4e3a5fc4-323d-4a09-8c72-f46d04b0eeb7

Approved on: 2022-07-05

Published on: 2022-09-06

HGVS expressions

NM_001110792.2:c.1001C>T

NM_001110792.2(MECP2):c.1001C>T (p.Pro334Leu)

NC_000023.11:g.154030863G>A

CM000685.2:g.154030863G>A

NC_000023.10:g.153296314G>A

CM000685.1:g.153296314G>A

NC_000023.9:g.152949508G>A

NG_007107.2:g.111265C>T

NG_007107.3:g.111241C>T

ENST00000303391.11:c.965C>T

ENST00000453960.7:c.1001C>T

ENST00000637917.1:n.139C>T

ENST00000303391.10:c.965C>T

ENST00000407218.5:c.*337C>T

ENST00000453960.6:c.1001C>T

ENST00000619732.4:c.965C>T

ENST00000622433.4:c.951C>T

ENST00000628176.2:c.*337C>T

NM_001110792.1:c.1001C>T

NM_001316337.1:c.686C>T

NM_004992.3:c.965C>T

NM_001316337.2:c.686C>T

NM_001369391.2:c.686C>T

NM_001369392.2:c.686C>T

NM_001369393.2:c.686C>T

NM_001369394.1:c.686C>T

NM_001369394.2:c.686C>T

NM_001386137.1:c.296C>T

NM_001386138.1:c.296C>T

NM_001386139.1:c.296C>T

NM_004992.4:c.965C>T

Pathogenic

PM2_Supporting PM6_Strong PS4 PP4 PM5

BP4 PP3 PM1

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 c.965C>T p.(Pro322Leu) variant in MECP2 (NM_004992.3) is absent from gnomAD (PM2_supporting). The p.(Pro322Leu) variant has been observed in at least 5 individuals with Rett syndrome (PMID: 10814718, 19722030, 17089071, 16672765, 11402105, 16473305) (PS4, PP4), where it has been reported in as de novo occurrences (biological parentage unconfirmed) in at least 2 individuals (PMID 10814718, 11402105) (PM6_strong). Multiple missense variants have been previously identified within this codon, at least one of which is classified as pathogenic; this indicates that this residue is critical to the function of the protein (PMID 10814719, 16966553, 16225173, 32820509) (PM5). In summary, the c.965C>T p.(Pro322Leu) variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS4, PM6_strong, PP4, PM5).

PM2_Supporting

The p.Pro322Leu variant in MECP2 is absent from gnomAD (PM2_supporting).

PM6_Strong

The p.Pro322Leu variant in MECP2 has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with Rett syndrome (PMID 10814718, 11402105) (PM6_strong).

PS4

The p.Pro322Leu variant has been observed in at least 5 individuals with Rett syndrome (PMID: 10814718, 19722030, 17089071, 16672765, 11402105, 16473305) (PS4).

PP4

The p.Pro322Leu variant in MECP2 has been reported in individuals with a clinical phenotype suggestive of Rett syndrome (PMID: 10814718, 19722030, 17089071, 16672765, 11402105, 16473305) (PP4).

PM5

Multiple missense variants have been previously identified within this codon, at least one of which is classified as pathogenic; this indicates that this residue is critical to the function of the protein (PMID 10814719, 16966553, 16225173, 32820509) (PM5).

BP4

Computational prediction analysis tools are inconclusive for this variant.

PP3

Computational prediction analysis tools are inconclusive for this variant.

PM1

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

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.