NM_001110792.2(MECP2):c.710C>G (p.Pro237Arg) AND Rett syndrome

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Mar 22, 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:: RCV000133193.7

Allele description [Variation Report for NM_001110792.2(MECP2):c.710C>G (p.Pro237Arg)]

NM_001110792.2(MECP2):c.710C>G (p.Pro237Arg)

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.710C>G (p.Pro237Arg)

Other names:

NM_001110792.2(MECP2):c.710C>G; p.Pro237Arg

HGVS:

NC_000023.11:g.154031154G>C
NG_007107.3:g.110950C>G
NM_001110792.2:c.710C>GMANE SELECT
NM_001316337.2:c.395C>G
NM_001369391.2:c.395C>G
NM_001369392.2:c.395C>G
NM_001369393.2:c.395C>G
NM_001369394.2:c.395C>G
NM_001386137.1:c.5C>G
NM_001386138.1:c.5C>G
NM_001386139.1:c.5C>G
NM_004992.4:c.674C>G
NP_001104262.1:p.Pro237Arg
NP_001303266.1:p.Pro132Arg
NP_001356320.1:p.Pro132Arg
NP_001356321.1:p.Pro132Arg
NP_001356322.1:p.Pro132Arg
NP_001356323.1:p.Pro132Arg
NP_001373066.1:p.Pro2Arg
NP_001373067.1:p.Pro2Arg
NP_001373068.1:p.Pro2Arg
NP_004983.1:p.Pro225Arg
NP_004983.1:p.Pro225Arg
LRG_764t1:c.710C>G
LRG_764t2:c.674C>G
AJ132917.1:c.674C>G
LRG_764:g.110950C>G
LRG_764p1:p.Pro237Arg
LRG_764p2:p.Pro225Arg
NC_000023.10:g.153296605G>C
NG_007107.2:g.110974C>G
NM_004992.3:c.674C>G
P51608:p.Pro225Arg

Protein change:

P132R

Links:

UniProtKB: P51608#VAR_018198; dbSNP: rs61749715

NCBI 1000 Genomes Browser:

rs61749715

Molecular consequence:

NM_001110792.2:c.710C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001316337.2:c.395C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369391.2:c.395C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369392.2:c.395C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369393.2:c.395C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369394.2:c.395C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386137.1:c.5C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386138.1:c.5C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386139.1:c.5C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004992.4:c.674C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

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wc44b11.x1 NCI_CGAP_Pr28 Homo sapiens cDNA clone IMAGE:2321469 3', mRNA sequence
wc44b11.x1 NCI_CGAP_Pr28 Homo sapiens cDNA clone IMAGE:2321469 3', mRNA sequence
gi|4874884|gnl|dbEST|2568807|gb|AI6 .1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000188191	RettBASE	no assertion criteria provided	Pathogenic (May 18, 2012)	de novo, unknown	curation	PubMed (12) [See all records that cite these PMIDs] 10854091, 11245712, 11524741, 12075485, 12111643, 12180070, 16473305, 16690727, 17089071, 17387578, 21160487, 21954873
SCV001427577	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	no assertion criteria provided	Likely pathogenic (Jan 1, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004013295	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 14, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004808878	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Pathogenic (Mar 22, 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	2	not provided	not provided	2	No	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	15	not provided	not provided	15	No	clinical testing, curation
not provided	unknown	unknown	1	not provided	not provided	1	No	curation

Citations

PubMed

Preserved speech variant is allelic of classic Rett syndrome.

De Bona C, Zappella M, Hayek G, Meloni I, Vitelli F, Bruttini M, Cusano R, Loffredo P, Longo I, Renieri A.

Eur J Hum Genet. 2000 May;8(5):325-30.

PubMed [citation]

PMID:: 10854091

MECP2 gene analysis in classical Rett syndrome and in patients with Rett-like features.

Auranen M, Vanhala R, Vosman M, Levander M, Varilo T, Hietala M, Riikonen R, Peltonen L, Järvelä I.

Neurology. 2001 Mar 13;56(5):611-7.

PubMed [citation]

PMID:: 11245712

See all PubMed Citations (14)

Details of each submission

From RettBASE, SCV000188191.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	No	curation	PubMed (12)
2	not provided	1	not provided	not provided	curation	PubMed (12)
3	not provided	1	not provided	not provided	curation	PubMed (12)
4	not provided	1	not provided	not provided	curation	PubMed (12)
5	not provided	1	not provided	not provided	curation	PubMed (12)
6	not provided	1	not provided	No	curation	PubMed (12)
7	not provided	1	not provided	not provided	curation	PubMed (12)
8	not provided	1	not provided	No	curation	PubMed (12)
9	not provided	1	not provided	not provided	curation	PubMed (12)
10	not provided	1	not provided	No	curation	PubMed (12)
11	not provided	1	not provided	No	curation	PubMed (12)
12	not provided	1	not provided	not provided	curation	PubMed (12)
13	not provided	1	not provided	not provided	curation	PubMed (12)
14	not provided	1	not provided	No	curation	PubMed (12)
15	not provided	1	not provided	No	curation	PubMed (12)
16	not provided	1	not provided	No	curation	PubMed (12)
17	not provided	1	not provided	not provided	curation	PubMed (12)
18	not provided	1	not provided	not provided	curation	PubMed (12)

Description

"Not known"

PubMed [ID: 12075485]

Rett syndrome - atypical

Rett syndrome - Classical

"Rett syndrome - Not certain"

PubMed [ID: 10854091]

"Rett syndrome - not certain"

PubMed [ID: 11245712]

"Rett syndrome - not certain"

PubMed [ID: 11524741]

"Rett syndrome - Not certain"

PubMed [ID: 12075485]

"Rett syndrome - Not certain"

PubMed [ID: 12075485]

"Rett syndrome - classical"

PubMed [ID: 12111643]

"Rett syndrome - Not certain"

PubMed [ID: 12180070]

"Rett syndrome - not certain"

PubMed [ID: 16473305]

"Rett syndrome - not certain"

PubMed [ID: 16473305]

"Rett syndrome - classical"

PubMed [ID: 16690727]

"Rett syndrome - Classical"

PubMed [ID: 17089071]

"Rett syndrome - not certain"

PubMed [ID: 17387578]

"Rett syndrome - Not certain"

PubMed [ID: 21160487]

"Rett syndrome - Classical"

PubMed [ID: 21954873]

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	1	Blood	not provided		1	not provided	not provided	not provided
2	unknown	yes	1	blood	not provided		1	not provided	not provided	not provided
3	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
4	de novo	yes	1	Blood	not provided		1	not provided	not provided	not provided
5	unknown	yes	1	Blood	not provided		1	not provided	not provided	not provided
6	unknown	yes	1	blood	not provided		1	not provided	not provided	not provided
7	unknown	yes	1	blood	not provided		1	not provided	not provided	not provided
8	unknown	yes	1	Blood	not provided		1	not provided	not provided	not provided
9	unknown	yes	1	Blood	not provided		1	not provided	not provided	not provided
10	unknown	yes	1	blood	not provided		1	not provided	not provided	not provided
11	unknown	yes	1	Blood	not provided		1	not provided	not provided	not provided
12	unknown	yes	1	blood	not provided		1	not provided	not provided	not provided
13	unknown	yes	1	blood	not provided		1	not provided	not provided	not provided
14	unknown	yes	1	blood	not provided		1	not provided	not provided	not provided
15	unknown	yes	1	blood	not provided		1	not provided	not provided	not provided
16	de novo	yes	1	blood	not provided		1	not provided	not provided	not provided
17	unknown	yes	1	Blood	not provided		1	not provided	not provided	not provided
18	unknown	yes	1	Blood or skin	not provided		1	not provided	not provided	not provided

From Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille, SCV001427577.1

#	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	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV004013295.1

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

Description

PS2, PS3, PS4, PM2, PP3

#	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 Centre for Population Genomics, CPG, SCV004808878.1

#	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: This variant has been identified as a de novo occurrence in at least 2 individuals with Rett syndrome, without confirmation of paternity and maternity (PM6_Strong).(PMID: 17089071, 10767337). Has been observed in at least 5 individuals with phenotypes consistent with MECP2-related disease (PS4). (PMID: 31427717, 17407838, 17387578, 17089071, 16473305, 19133691, 18842453, 10767337, 11245712). Computational prediction analysis tools suggests a deleterious impact (REVEL score>= 0.75) (PP3). This variant is absent from gnomAD v4 (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: Nov 10, 2024

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