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NM_001110792.2(MECP2):c.509C>T (p.Thr170Met) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 7, 2020
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000623451.12

Allele description [Variation Report for NM_001110792.2(MECP2):c.509C>T (p.Thr170Met)]

NM_001110792.2(MECP2):c.509C>T (p.Thr170Met)

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.509C>T (p.Thr170Met)
Other names:
p.T158M:ACG>ATG; NM_001110792.2(MECP2):c.509C>T; p.Thr170Met
HGVS:
  • NC_000023.11:g.154031355G>A
  • NG_007107.3:g.110749C>T
  • NM_001110792.2:c.509C>TMANE SELECT
  • NM_001316337.2:c.194C>T
  • NM_001369391.2:c.194C>T
  • NM_001369392.2:c.194C>T
  • NM_001369393.2:c.194C>T
  • NM_001369394.2:c.194C>T
  • NM_001386137.1:c.-129+41C>T
  • NM_001386138.1:c.-129+41C>T
  • NM_001386139.1:c.-129+41C>T
  • NM_004992.4:c.473C>T
  • NP_001104262.1:p.Thr170Met
  • NP_001303266.1:p.Thr65Met
  • NP_001356320.1:p.Thr65Met
  • NP_001356321.1:p.Thr65Met
  • NP_001356322.1:p.Thr65Met
  • NP_001356323.1:p.Thr65Met
  • NP_004983.1:p.Thr158Met
  • NP_004983.1:p.Thr158Met
  • LRG_764t1:c.509C>T
  • LRG_764t2:c.473C>T
  • AJ132917.1:c.473C>T
  • LRG_764:g.110749C>T
  • LRG_764p1:p.Thr170Met
  • LRG_764p2:p.Thr158Met
  • NC_000023.10:g.153296806G>A
  • NG_007107.2:g.110773C>T
  • NM_001110792.1:c.509C>T
  • NM_001316337.2:c.194C>T
  • NM_001369391.2:c.194C>T
  • NM_004992.3:c.473C>T
  • NM_004992.3:c.[473C>T]
  • NM_004992.4:c.473C>T
  • P51608:p.Thr158Met
  • p.(Thr158Met)
Protein change:
T158M; THR158MET
Links:
UniProtKB: P51608#VAR_010275; OMIM: 300005.0007; dbSNP: rs28934906
NCBI 1000 Genomes Browser:
rs28934906
Molecular consequence:
  • NM_001386137.1:c.-129+41C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001386138.1:c.-129+41C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001386139.1:c.-129+41C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001110792.2:c.509C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001316337.2:c.194C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369391.2:c.194C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369392.2:c.194C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369393.2:c.194C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369394.2:c.194C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004992.4:c.473C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000845943Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Oct 7, 2020) 		germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2.

Nan X, Meehan RR, Bird A.

Nucleic Acids Res. 1993 Oct 25;21(21):4886-92.

PubMed [citation]
PMID:
8177735
PMCID:
PMC311401

Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.

Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY.

Nat Genet. 1999 Oct;23(2):185-8.

PubMed [citation]
PMID:
10508514
See all PubMed Citations (12)

Details of each submission

From Ambry Genetics, SCV000845943.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

The c.473C>T (p.T158M) alteration is located in exon 4 (coding exon 3) of the MECP2 gene. This alteration results from a C to T substitution at nucleotide position 473, causing the threonine (T) at amino acid position 158 to be replaced by a methionine (M). Based on data from the Genome Aggregation Database (gnomAD), the MECP2 c.473C>T alteration was not observed, with coverage at this position. The MECP2 c.473C>T (p.T158M) alteration is one of the most common pathogenic variants in MECP2, occurring at a CpG hotspot (Amir, 1999). This alteration has been identified in female patients with both classical Rett syndrome as well as atypical Rett syndrome; more mildly affected individuals have also been described with this alteration (Amir, 1999; Buyse, 2000; Huppke, 2000; Auranen, 2001; Bao, 2013; Suter, 2014). Functional analysis demonstrated that the p.T158M alteration moderately affects MeCP2's ability to bind to methylated DNA and impair selectivity for methylated DNA (Ballestar, 2000; Yusufzai, 2000). The p.T158M alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

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

Last Updated: Nov 3, 2024