NM_170707.4(LMNA):c.391C>T (p.Gln131Ter) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 8, 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:: RCV000653933.6

Allele description [Variation Report for NM_170707.4(LMNA):c.391C>T (p.Gln131Ter)]

NM_170707.4(LMNA):c.391C>T (p.Gln131Ter)

Genes:

LOC126805877:MED14-independent group 3 enhancer GRCh37_chr1:156099693-156100892 [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.391C>T (p.Gln131Ter)

HGVS:

NC_000001.11:g.156130651C>T
NG_008692.2:g.53079C>T
NM_001257374.3:c.55C>T
NM_001282624.2:c.148C>T
NM_001282625.2:c.391C>T
NM_001282626.2:c.391C>T
NM_005572.4:c.391C>T
NM_170707.4:c.391C>TMANE SELECT
NM_170708.4:c.391C>T
NP_001244303.1:p.Gln19Ter
NP_001269553.1:p.Gln50Ter
NP_001269554.1:p.Gln131Ter
NP_001269555.1:p.Gln131Ter
NP_005563.1:p.Gln131Ter
NP_733821.1:p.Gln131Ter
NP_733822.1:p.Gln131Ter
LRG_254:g.53079C>T
NC_000001.10:g.156100442C>T
NM_170707.3:c.391C>T

Protein change:

Q131*

Links:

dbSNP: rs1553264593

NCBI 1000 Genomes Browser:

rs1553264593

Molecular consequence:

NM_001257374.3:c.55C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282624.2:c.148C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282625.2:c.391C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282626.2:c.391C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005572.4:c.391C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_170707.4:c.391C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_170708.4:c.391C>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

Recent activity

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SUMO-activating enzyme subunit 1 isoform a [Mus musculus]
SUMO-activating enzyme subunit 1 isoform a [Mus musculus]
gi|552953709|ref|NP_001272820.1|

Protein
Aicda activation-induced cytidine deaminase [Mus musculus]
Aicda activation-induced cytidine deaminase [Mus musculus]
Gene ID:11628

Gene
11628[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000775823	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 8, 2023)	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

SCV000775823

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 8, 2023)

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, SCV000775823.5

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 543228). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln131*) in the LMNA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LMNA are known to be pathogenic (PMID: 18585512, 18926329).

#	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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