NM_001110792.2(MECP2):c.722C>A (p.Ser241Ter) AND Rett syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 15, 2024
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:: RCV000193948.9

Allele description [Variation Report for NM_001110792.2(MECP2):c.722C>A (p.Ser241Ter)]

NM_001110792.2(MECP2):c.722C>A (p.Ser241Ter)

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.722C>A (p.Ser241Ter)

Other names:

NM_001110792.2(MECP2):c.722C>A; p.Ser241Ter

HGVS:

NC_000023.11:g.154031142G>T
NG_007107.3:g.110962C>A
NM_001110792.2:c.722C>AMANE SELECT
NM_001316337.2:c.407C>A
NM_001369391.2:c.407C>A
NM_001369392.2:c.407C>A
NM_001369393.2:c.407C>A
NM_001369394.2:c.407C>A
NM_001386137.1:c.17C>A
NM_001386138.1:c.17C>A
NM_001386139.1:c.17C>A
NM_004992.4:c.686C>A
NP_001104262.1:p.Ser241Ter
NP_001303266.1:p.Ser136Ter
NP_001356320.1:p.Ser136Ter
NP_001356321.1:p.Ser136Ter
NP_001356322.1:p.Ser136Ter
NP_001356323.1:p.Ser136Ter
NP_001373066.1:p.Ser6Ter
NP_001373067.1:p.Ser6Ter
NP_001373068.1:p.Ser6Ter
NP_004983.1:p.Ser229Ter
NP_004983.1:p.Ser229Ter
LRG_764t1:c.722C>A
LRG_764t2:c.686C>A
AJ132917.1:c.686C>A
LRG_764:g.110962C>A
LRG_764p1:p.Ser241Ter
LRG_764p2:p.Ser229Ter
NC_000023.10:g.153296593G>T
NG_007107.2:g.110986C>A
NM_004992.3:c.686C>A

Protein change:

S136*

Links:

dbSNP: rs61749739

NCBI 1000 Genomes Browser:

rs61749739

Molecular consequence:

NM_001110792.2:c.722C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001316337.2:c.407C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369391.2:c.407C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369392.2:c.407C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369393.2:c.407C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369394.2:c.407C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001386137.1:c.17C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001386138.1:c.17C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001386139.1:c.17C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_004992.4:c.686C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

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Chain A, Uncharacterized protein
Chain A, Uncharacterized protein
gi|409973857|pdb|4FR9|A

Protein
PREDICTED: Mus musculus keratin 10 (Krt10), transcript variant X1, mRNA
PREDICTED: Mus musculus keratin 10 (Krt10), transcript variant X1, mRNA
gi|1907080159|ref|XM_011248768.3|

Nucleotide
50S ribosomal protein L14 [Hydrogenobacter thermophilus]
50S ribosomal protein L14 [Hydrogenobacter thermophilus]
gi|502728370|ref|WP_012963354.1|

Protein
Rattus norvegicus transmembrane protein 126A (Tmem126a), mRNA
Rattus norvegicus transmembrane protein 126A (Tmem126a), mRNA
gi|1996191907|ref|NM_001011557.2|

Nucleotide
Ligusticum sikiangense voucher KD small subunit ribosomal RNA gene, partial sequ...
Ligusticum sikiangense voucher KD small subunit ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and large subunit ribosomal RNA gene, partial sequence
gi|2240424521|gb|ON543389.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000247985	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2007)	Pathogenic (Feb 8, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000899198	Biochemistry Laboratory of CDMU, Chengde Medical University	no assertion criteria provided (ACMG Guidelines, 2015)	Pathogenic	de novo	case-control	PubMed (1) [See all records that cite this PMID]
SCV004808765	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Pathogenic (Mar 15, 2024)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000247985

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2007)

Pathogenic
(Feb 8, 2013)

germline

clinical testing

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

SCV000899198

Biochemistry Laboratory of CDMU, Chengde Medical University

no assertion criteria provided

(ACMG Guidelines, 2015)

Pathogenic

de novo

case-control

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

SCV004808765

Centre for Population Genomics, CPG

criteria provided, single submitter

(McKnight et al. (Hum Mutat. 2022))

Pathogenic
(Mar 15, 2024)

germline

curation

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	case-control
not provided	germline	yes	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	curation

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee..

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

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

See all PubMed Citations (3)

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV000247985.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Biochemistry Laboratory of CDMU, Chengde Medical University, SCV000899198.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	case-control	PubMed (1)

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

From Centre for Population Genomics, CPG, SCV004808765.1

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

Description

This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). This variant has been identified as a de novo occurrence in an individual with Rett syndrome without confirmation of paternity and maternity (PM6). PMID 31178897. This variant is absent from gnomAD (PM2_Supporting).

#	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: Apr 15, 2024

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