NM_001110792.2(MECP2):c.334C>G (p.Leu112Val) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 24, 2023
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:: RCV000498874.26

Allele description [Variation Report for NM_001110792.2(MECP2):c.334C>G (p.Leu112Val)]

NM_001110792.2(MECP2):c.334C>G (p.Leu112Val)

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.334C>G (p.Leu112Val)

Other names:

NM_001110792.2(MECP2):c.334C>G; p.Leu112Val

HGVS:

NC_000023.11:g.154032286G>C
NG_007107.3:g.109818C>G
NM_001110792.2:c.334C>GMANE SELECT
NM_001316337.2:c.19C>G
NM_001369391.2:c.19C>G
NM_001369392.2:c.19C>G
NM_001369393.2:c.19C>G
NM_001369394.2:c.19C>G
NM_001386137.1:c.-263C>G
NM_001386138.1:c.-263C>G
NM_001386139.1:c.-263C>G
NM_004992.4:c.298C>G
NP_001104262.1:p.Leu112Val
NP_001303266.1:p.Leu7Val
NP_001356320.1:p.Leu7Val
NP_001356321.1:p.Leu7Val
NP_001356322.1:p.Leu7Val
NP_001356323.1:p.Leu7Val
NP_004983.1:p.Leu100Val
NP_004983.1:p.Leu100Val
LRG_764t1:c.334C>G
LRG_764t2:c.298C>G
AJ132917.1:c.298C>G
LRG_764:g.109818C>G
LRG_764p1:p.Leu112Val
LRG_764p2:p.Leu100Val
NC_000023.10:g.153297737G>C
NG_007107.2:g.109842C>G
NM_004992.3:c.298C>G
P51608:p.Leu100Val

Protein change:

L100V; LEU100VAL

Links:

UniProtKB: P51608#VAR_017462; OMIM: 300005.0027; dbSNP: rs28935168

NCBI 1000 Genomes Browser:

rs28935168

Molecular consequence:

NM_001386137.1:c.-263C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-263C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-263C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.334C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001316337.2:c.19C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369391.2:c.19C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369392.2:c.19C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369393.2:c.19C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369394.2:c.19C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004992.4:c.298C>G - 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
SCV000589568	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 24, 2023)	germline	clinical testing	Citation Link,
SCV001248058	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Dec 1, 2018)	germline	clinical testing	Citation Link,
SCV001447618	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	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

SCV000589568

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 24, 2023)

germline

clinical testing

Citation Link,

SCV001248058

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Dec 1, 2018)

germline

clinical testing

Citation Link,

SCV001447618

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 23, 2020)

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	germline	yes	1	not provided	not provided	1	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 GeneDx, SCV000589568.4

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

Description

Published functional studies demonstrate that this variant leads to an unstable MECP2 protein (Kucukkal et al., 2015; Yang et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 12966522, 16672765, 21831886, 12843318, 28351539, 26239053, 27356039, 11055898, 22476991, 32472557, 11913567, 26418480, 12673788)

#	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, SCV001248058.26

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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001447618.1

#	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	1	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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