U.S. flag

An official website of the United States government

NM_001110792.2(MECP2):c.799C>T (p.Arg267Ter) AND multiple conditions

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jan 10, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000515183.11

Allele description [Variation Report for NM_001110792.2(MECP2):c.799C>T (p.Arg267Ter)]

NM_001110792.2(MECP2):c.799C>T (p.Arg267Ter)

Gene:
MECP2:methyl-CpG binding protein 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_001110792.2(MECP2):c.799C>T (p.Arg267Ter)
Other names:
p.R255*:CGA>TGA; NM_001110792.2(MECP2):c.799C>T; p.Arg267Ter
HGVS:
  • NC_000023.11:g.154031065G>A
  • NG_007107.3:g.111039C>T
  • NM_001110792.2:c.799C>TMANE SELECT
  • NM_001316337.2:c.484C>T
  • NM_001369391.2:c.484C>T
  • NM_001369392.2:c.484C>T
  • NM_001369393.2:c.484C>T
  • NM_001369394.2:c.484C>T
  • NM_001386137.1:c.94C>T
  • NM_001386138.1:c.94C>T
  • NM_001386139.1:c.94C>T
  • NM_004992.4:c.763C>T
  • NP_001104262.1:p.Arg267Ter
  • NP_001303266.1:p.Arg162Ter
  • NP_001356320.1:p.Arg162Ter
  • NP_001356321.1:p.Arg162Ter
  • NP_001356322.1:p.Arg162Ter
  • NP_001356323.1:p.Arg162Ter
  • NP_001373066.1:p.Arg32Ter
  • NP_001373067.1:p.Arg32Ter
  • NP_001373068.1:p.Arg32Ter
  • NP_004983.1:p.Arg255Ter
  • NP_004983.1:p.Arg255Ter
  • LRG_764t1:c.799C>T
  • LRG_764t2:c.763C>T
  • AJ132917.1:c.763C>T
  • LRG_764:g.111039C>T
  • LRG_764p1:p.Arg267Ter
  • LRG_764p2:p.Arg255Ter
  • NC_000023.10:g.153296516G>A
  • NG_007107.2:g.111063C>T
  • NM_001110792.1:c.799C>T
  • NM_004992.3:c.763C>T
  • NM_004992.4:c.763C>T
  • NP_004983.1:p.Arg255*
  • p.(Arg255*)
  • p.Arg255X
Protein change:
R162*; ARG255TER
Links:
OMIM: 300005.0021; dbSNP: rs61749721
NCBI 1000 Genomes Browser:
rs61749721
Molecular consequence:
  • NM_001110792.2:c.799C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001316337.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001369391.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001369392.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001369393.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001369394.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001386137.1:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001386138.1:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001386139.1:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004992.4:c.763C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Severe neonatal-onset encephalopathy with microcephaly
Synonyms:
Encephalopathy, neonatal severe; Encephalopathy, neonatal severe, due to MECP2 mutations
Identifiers:
MONDO: MONDO:0010397; MedGen: C1968556; Orphanet: 209370; OMIM: 300673
Name:
Syndromic X-linked intellectual disability Lubs type (MRXSL)
Synonyms:
MENTAL RETARDATION, X-LINKED, WITH RECURRENT RESPIRATORY INFECTIONS; Lubs X-linked mental retardation syndrome; XLMR syndrome, Lubs type; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010283; MedGen: C1846058; OMIM: 300260
Name:
X-linked intellectual disability-psychosis-macroorchidism syndrome (MRXS13)
Synonyms:
INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC 13; PPM-X syndrome
Identifiers:
MONDO: MONDO:0010235; MedGen: C0796222; Orphanet: 3077; OMIM: 300055
Name:
Rett syndrome (RTT)
Synonyms:
Autism, dementia, ataxia, and loss of purposeful hand use; Rett's disorder
Identifiers:
MONDO: MONDO:0010726; MedGen: C0035372; Orphanet: 3095; Orphanet: 778; OMIM: 312750
Name:
Autism, susceptibility to, X-linked 3 (AUTSX3)
Synonyms:
Austism susceptibility, X-linked; Autism susceptibility, X-linked 3
Identifiers:
MONDO: MONDO:0010342; MedGen: C1845336; OMIM: 300496

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000611281Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(May 18, 2017) 		unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003920190Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jan 10, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV000611281.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920190.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

MECP2 NM_004992.3 exon 4 p.Arg255* (c.763C>T): This variant has been reported in the literature in numerous (n>100) individuals with Rett syndrome (select publications: Amir 1999 PMID:10508514, Knight 2013 PMID:23270700, McRae 2017 PMID:28135719, Hettiarachchi 2019 PMID:31535341, RettBASE). This variant is not present in large control databases but is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID:11829). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. In addition, functional studies have shown a deleterious effect of this variant (Yusufzai 2000 PMID:11058114, Delepine 2013 PMID:23238081, Pitcher 2015 PMID:25634563). However, these studies may not accurately represent in vivo biological function. The vast majority of pathogenic variants are identified in exon 4 which encodes for the methyl binding domain and transcription repression domain. This variant creates a premature stop at this codon within exon 4 which results in an absent or abnormal protein. Loss of function variants are a known mechanism of disease for this gene (Philippe 2006 16473305). In summary, this variant is classified as pathogenic based on the data above.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 17, 2024