NM_000117.3(EMD):c.215A>T (p.Asp72Val) AND X-linked Emery-Dreifuss muscular dystrophy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 13, 2023
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:: RCV001852357.7

Allele description [Variation Report for NM_000117.3(EMD):c.215A>T (p.Asp72Val)]

NM_000117.3(EMD):c.215A>T (p.Asp72Val)

Gene:

EMD:emerin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000117.3(EMD):c.215A>T (p.Asp72Val)

Other names:

p.D72V:GAT>GTT

HGVS:

NC_000023.11:g.154379969A>T
NG_008677.1:g.10534A>T
NM_000117.3:c.215A>TMANE SELECT
NP_000108.1:p.Asp72Val
NP_000108.1:p.Asp72Val
LRG_745t1:c.215A>T
LRG_745:g.10534A>T
LRG_745p1:p.Asp72Val
NC_000023.10:g.153608329A>T
NM_000117.2:c.215A>T

Protein change:

D72V

Links:

dbSNP: rs794729021

NCBI 1000 Genomes Browser:

rs794729021

Molecular consequence:

NM_000117.3:c.215A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: X-linked Emery-Dreifuss muscular dystrophy
Synonyms:: Muscular dystrophy, tardive Emery-Dreifuss type, with contractures
Identifiers:: MONDO: MONDO:0010680; MedGen: C0751337; Orphanet: 261; Orphanet: 98863

Recent activity

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Homo sapiens, clone IMAGE:5530198, mRNA
Homo sapiens, clone IMAGE:5530198, mRNA
gi|28703950|gb|BC047293.1|

Nucleotide
essv6681384 (3)
dbVar

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002145907	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 13, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12872622, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002145907

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 13, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

[DNA-diagnosis of Emery-Dreifuss muscular dystrophy].

Tverskaia SM, Rudenskaia GE, Chukhrova AL, Poliakov AV.

Zh Nevrol Psikhiatr Im S S Korsakova. 2003;103(6):25-8. Russian.

PubMed [citation]

PMID:: 12872622

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, SCV002145907.3

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 72 of the EMD protein (p.Asp72Val). This variant is present in population databases (rs794729021, gnomAD 0.005%). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 12872622). ClinVar contains an entry for this variant (Variation ID: 201783). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EMD protein function with a negative predictive value of 80%. 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

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