NM_016156.6(MTMR2):c.506G>A (p.Gly169Glu) AND Charcot-Marie-Tooth disease type 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 26, 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:: RCV001365408.7

Allele description [Variation Report for NM_016156.6(MTMR2):c.506G>A (p.Gly169Glu)]

NM_016156.6(MTMR2):c.506G>A (p.Gly169Glu)

Gene:

MTMR2:myotubularin related protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q21

Genomic location:

Preferred name:

NM_016156.6(MTMR2):c.506G>A (p.Gly169Glu)

HGVS:

NC_000011.10:g.95858595C>T
NG_008333.1:g.70613G>A
NM_001243571.2:c.290G>A
NM_016156.6:c.506G>AMANE SELECT
NM_201278.3:c.290G>A
NM_201281.3:c.290G>A
NP_001230500.1:p.Gly97Glu
NP_057240.3:p.Gly169Glu
NP_958435.1:p.Gly97Glu
NP_958438.1:p.Gly97Glu
LRG_257:g.70613G>A
NC_000011.9:g.95591759C>T

Protein change:

G169E

Links:

dbSNP: rs1864296648

NCBI 1000 Genomes Browser:

rs1864296648

Molecular consequence:

NM_001243571.2:c.290G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016156.6:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201278.3:c.290G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201281.3:c.290G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 4
Synonyms:: Charcot-Marie-Tooth, Type 4
Identifiers:: MONDO: MONDO:0018995; MedGen: C4082197

Recent activity

Clear Turn Off Turn On

Chromosome neighbors for GEO Profiles (Select 6193361) (20)
GEO Profiles
Pre-mRNA splicing factor mutants at restrictive temperature: time course
Pre-mRNA splicing factor mutants at restrictive temperature: time course
Accession: GDS759

GEO DataSets
Related DataSets for GEO Profiles (Select 6193353) (1)
GEO DataSets
Related DataSets for GEO Profiles (Select 6193348) (1)
GEO DataSets

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001561679	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 26, 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

SCV001561679

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 26, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001561679.4

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

Description

This sequence change replaces glycine with glutamic acid at codon 169 of the MTMR2 protein (p.Gly169Glu). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MTMR2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine