NM_001110792.2(MECP2):c.352C>T (p.Arg118Trp) AND not provided

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Jan 7, 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:: RCV000255874.36

Allele description [Variation Report for NM_001110792.2(MECP2):c.352C>T (p.Arg118Trp)]

NM_001110792.2(MECP2):c.352C>T (p.Arg118Trp)

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.352C>T (p.Arg118Trp)

Other names:

NM_001110792.2(MECP2):c.352C>T; p.Arg118Trp

HGVS:

NC_000023.11:g.154032268G>A
NG_007107.3:g.109836C>T
NM_001110792.2:c.352C>TMANE SELECT
NM_001316337.2:c.37C>T
NM_001369391.2:c.37C>T
NM_001369392.2:c.37C>T
NM_001369393.2:c.37C>T
NM_001369394.2:c.37C>T
NM_001386137.1:c.-245C>T
NM_001386138.1:c.-245C>T
NM_001386139.1:c.-245C>T
NM_004992.4:c.316C>T
NP_001104262.1:p.Arg118Trp
NP_001303266.1:p.Arg13Trp
NP_001356320.1:p.Arg13Trp
NP_001356321.1:p.Arg13Trp
NP_001356322.1:p.Arg13Trp
NP_001356323.1:p.Arg13Trp
NP_004983.1:p.Arg106Trp
NP_004983.1:p.Arg106Trp
LRG_764t1:c.352C>T
LRG_764t2:c.316C>T
AJ132917.1:c.316C>T
LRG_764:g.109836C>T
LRG_764p1:p.Arg118Trp
LRG_764p2:p.Arg106Trp
NC_000023.10:g.153297719G>A
NG_007107.2:g.109860C>T
NM_004992.3:c.316C>T
P51608:p.Arg106Trp
p.R106W

Protein change:

R106W; ARG106TRP

Links:

UniProtKB: P51608#VAR_010272; OMIM: 300005.0008; dbSNP: rs28934907

NCBI 1000 Genomes Browser:

rs28934907

Molecular consequence:

NM_001386137.1:c.-245C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-245C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-245C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001316337.2:c.37C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369391.2:c.37C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369392.2:c.37C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369393.2:c.37C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369394.2:c.37C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004992.4:c.316C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000229062	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Mar 23, 2015)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10508514, 10852707, 18337588, 20098342 Citation Link,
SCV000321873	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 7, 2022)	germline	clinical testing	Citation Link,
SCV001246094	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Sep 1, 2021)	germline	clinical testing	Citation Link,
SCV001929902	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001951157	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV004220012	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Apr 16, 2012)	unknown	clinical testing	PubMed (29) [See all records that cite these PMIDs] 10508514, 10577905, 10745042, 10767337, 10991688, 10991689, 11055898, 11241840, 11269512, 11402105, 11738883, 12872250, 15057977, 27929079, 31958484, 31816669, 35606502, 36430969, 32472557, 24715477, 20098342, 23270700, 23421866, 21831886, 12843318, 11738866, 19442733, 20231667, 26467025

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	7	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Effects of Rett syndrome mutations of the methyl-CpG binding domain of the transcriptional repressor MeCP2 on selectivity for association with methylated DNA.

Ballestar E, Yusufzai TM, Wolffe AP.

Biochemistry. 2000 Jun 20;39(24):7100-6.

PubMed [citation]

PMID:: 10852707

Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome.

Neul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO, Zoghbi H, Percy A, Glaze DG.

Neurology. 2008 Apr 15;70(16):1313-21. doi: 10.1212/01.wnl.0000291011.54508.aa. Epub 2008 Mar 12.

PubMed [citation]

PMID:: 18337588
PMCID:: PMC2677974

See all PubMed Citations (31)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000229062.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (4)

#	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		2	not provided	not provided	not provided

From GeneDx, SCV000321873.10

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

Description

Reported as a common pathogenic variant in association with Rett syndrome (Amir et al., 1999; Vilchis et al., 2014; RettBASE); Published functional studies suggest it significantly impairs the binding of methylated DNA (Ballestar et al., 2000); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24715477, 20098342, 23270700, 25789914, 19442733, 19217433, 25942534, 25900226, 20231667, 21831886, 11058114, 10852707, 25814391, 26017205, 26379794, 26418480, 26175308, 26278631, 25914188, 25779967, 25659951, 26108439, 26003587, 11738866, 12843318, 27929079, 16077729, 29631775, 30202406, 30564305, 29655203, 10508514, 31095231, 28920956, 32730690, 32369273, 31130284, 33258288, 32105570, 32472557)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001246094.23

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	not provided	not provided	clinical testing	not provided

#	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		7	not provided	not provided	not provided

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001929902.1

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

#	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 Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001951157.1

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

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004220012.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (29)

Description

It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in multiple individuals with Rett syndrome (PMIDs: 27929079 (2022), 32472557 (2020), 23270700 (2013), 20231667 (2010), 20098342 (2010), 10508514 (1999)). Experimental studies have indicated that the variant is damaging to MECP2 protein function (PMIDs: 27929079 (2016), 21831886 (2011), 19442733 (2009), 12843318 (2003), 11738866 (2001)). Based on the available information, this variant is classified as pathogenic.

#	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

Last Updated: Jul 15, 2024

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