NM_170707.4(LMNA):c.4G>T (p.Glu2Ter) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 2018
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:: RCV000688289.6

Allele description [Variation Report for NM_170707.4(LMNA):c.4G>T (p.Glu2Ter)]

NM_170707.4(LMNA):c.4G>T (p.Glu2Ter)

Gene:

LMNA:lamin A/C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_170707.4(LMNA):c.4G>T (p.Glu2Ter)

HGVS:

NC_000001.11:g.156114922G>T
NG_008692.2:g.37350G>T
NM_001282625.2:c.4G>T
NM_001282626.2:c.4G>T
NM_005572.4:c.4G>T
NM_170707.4:c.4G>TMANE SELECT
NM_170708.4:c.4G>T
NP_001269554.1:p.Glu2Ter
NP_001269555.1:p.Glu2Ter
NP_005563.1:p.Glu2Ter
NP_733821.1:p.Glu2Ter
NP_733822.1:p.Glu2Ter
LRG_254t2:c.4G>T
LRG_254:g.37350G>T
NC_000001.10:g.156084713G>T
NM_170707.2:c.4G>T
NM_170707.3:c.4G>T

Protein change:

E2*

Links:

dbSNP: rs1558115754

NCBI 1000 Genomes Browser:

rs1558115754

Molecular consequence:

NM_001282625.2:c.4G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282626.2:c.4G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005572.4:c.4G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_170707.4:c.4G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_170708.4:c.4G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 2
Synonyms:: Charcot-Marie-Tooth, Type 2
Identifiers:: MONDO: MONDO:0018993; MedGen: C0270914

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000815894	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 29, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18585512, 18926329, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000815894

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 29, 2018)

germline

clinical testing

PubMed (3)
[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

Lamin A/C mutation analysis in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy.

Parks SB, Kushner JD, Nauman D, Burgess D, Ludwigsen S, Peterson A, Li D, Jakobs P, Litt M, Porter CB, Rahko PS, Hershberger RE.

Am Heart J. 2008 Jul;156(1):161-9. doi: 10.1016/j.ahj.2008.01.026. Epub 2008 Mar 12.

PubMed [citation]

PMID:: 18585512
PMCID:: PMC2527054

Long-term outcome and risk stratification in dilated cardiolaminopathies.

Pasotti M, Klersy C, Pilotto A, Marziliano N, Rapezzi C, Serio A, Mannarino S, Gambarin F, Favalli V, Grasso M, Agozzino M, Campana C, Gavazzi A, Febo O, Marini M, Landolina M, Mortara A, Piccolo G, Viganò M, Tavazzi L, Arbustini E.

J Am Coll Cardiol. 2008 Oct 7;52(15):1250-60. doi: 10.1016/j.jacc.2008.06.044.

PubMed [citation]

PMID:: 18926329

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000815894.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Glu2*) in the LMNA gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LMNA are known to be pathogenic (PMID: 18585512, 18926329). This variant has not been reported in the literature in individuals with LMNA-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database.

#	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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