NM_001110792.2(MECP2):c.916C>T (p.Arg306Ter) AND multiple conditions

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 21, 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:: RCV000515413.5

Allele description [Variation Report for NM_001110792.2(MECP2):c.916C>T (p.Arg306Ter)]

NM_001110792.2(MECP2):c.916C>T (p.Arg306Ter)

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.916C>T (p.Arg306Ter)

Other names:

NP_004983.1:p.Arg294*; p.R294X:CGA>TGA; NM_001110792.2(MECP2):c.916C>T

HGVS:

NC_000023.11:g.154030948G>A
NG_007107.3:g.111156C>T
NM_001110792.1(MECP2):c.916C>T
NM_001110792.2:c.916C>TMANE SELECT
NM_001316337.2:c.601C>T
NM_001369391.2:c.601C>T
NM_001369392.2:c.601C>T
NM_001369393.2:c.601C>T
NM_001369394.2:c.601C>T
NM_001386137.1:c.211C>T
NM_001386138.1:c.211C>T
NM_001386139.1:c.211C>T
NM_004992.4:c.880C>T
NP_001104262.1:p.Arg306Ter
NP_001303266.1:p.Arg201Ter
NP_001356320.1:p.Arg201Ter
NP_001356321.1:p.Arg201Ter
NP_001356322.1:p.Arg201Ter
NP_001356323.1:p.Arg201Ter
NP_001373066.1:p.Arg71Ter
NP_001373067.1:p.Arg71Ter
NP_001373068.1:p.Arg71Ter
NP_004983.1:p.Arg294Ter
NP_004983.1:p.Arg294Ter
LRG_764t1:c.916C>T
LRG_764t2:c.880C>T
AJ132917.1:c.880C>T
LRG_764:g.111156C>T
LRG_764p1:p.Arg306Ter
LRG_764p2:p.Arg294Ter
NC_000023.10:g.153296399G>A
NG_007107.2:g.111180C>T
NM_001110792.1(MECP2):c.916C>T
NM_001110792.1:c.916C>T
NM_001110792.2:c.916C>T
NM_004992.3:c.880C>T
NM_004992.3:c.[880C>T]
p.Arg294X
p.Arg306Ter
p.R294X

Protein change:

R201*; ARG294TER

Links:

OMIM: 300005.0011; dbSNP: rs61751362

NCBI 1000 Genomes Browser:

rs61751362

Molecular consequence:

NM_001110792.2:c.916C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001316337.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369391.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369392.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369393.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369394.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386137.1:c.211C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386138.1:c.211C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386139.1:c.211C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004992.4:c.880C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000611280	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 21, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003920186	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000611280

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 21, 2022)

unknown

clinical testing

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

SCV003920186

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 30, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV000611280.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920186.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant has been reported in the literature in numerous individuals with Rett syndrome, including males, and as de novo in at least 1 individual with autism spectrum disorder (ASD) (Selected publications: Cheadler 2000 PMID:10767337, Yamashita 2001 PMID:11738864, Jian 2005 PMID:16077729, Lundvall 2006 PMID:17236109, Stachon 2007 PMID:17420824, Wen 2017 PMID:28785396). This variant is not present in large control databases. This variant is present in ClinVar, with several labs classifying this variant as pathogenic or likely pathogenic (Variation ID:11819). Functional studies support that this variant will impact the protein, suggesting repression of transcription and instability (Yusufzai 2000 PMID:11058114). This variant is predicted to cause a stopgain at this codon, resulting in protein truncation or abnormal protein. Of note, this variant occurs within the last exon of this gene; due to its position, it is possible that this protein may escape nonsense mediated decay. However, the vast majority of pathogenic variants in this gene (including this variant) are identified in exon 4 which encodes for the methyl binding domain and transcription repression domain. Loss of function has been established for this gene, but missense variants have been described as pathogenic as well (Philippe 2006 PMID:16473305). In summary, this variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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