NM_170707.4(LMNA):c.1146C>T (p.Gly382=) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 27, 2024
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:: RCV000468865.7

Allele description [Variation Report for NM_170707.4(LMNA):c.1146C>T (p.Gly382=)]

NM_170707.4(LMNA):c.1146C>T (p.Gly382=)

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.1146C>T (p.Gly382=)

Other names:

p.G382G:GGC>GGT

HGVS:

NC_000001.11:g.156136110C>T
NG_008692.2:g.58538C>T
NM_001257374.3:c.810C>T
NM_001282624.2:c.903C>T
NM_001282625.2:c.1146C>T
NM_001282626.2:c.1146C>T
NM_005572.4:c.1146C>T
NM_170707.4:c.1146C>TMANE SELECT
NM_170708.4:c.1146C>T
NP_001244303.1:p.Gly270=
NP_001269553.1:p.Gly301=
NP_001269554.1:p.Gly382=
NP_001269555.1:p.Gly382=
NP_005563.1:p.Gly382=
NP_733821.1:p.Gly382=
NP_733822.1:p.Gly382=
LRG_254t2:c.1146C>T
LRG_254:g.58538C>T
NC_000001.10:g.156105901C>T
NM_170707.2:c.1146C>T
NM_170707.3:c.1146C>T
c.1146C>T

Links:

dbSNP: rs57508089

NCBI 1000 Genomes Browser:

rs57508089

Molecular consequence:

NM_001257374.3:c.810C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001282624.2:c.903C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001282625.2:c.1146C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001282626.2:c.1146C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_005572.4:c.1146C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_170707.4:c.1146C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_170708.4:c.1146C>T - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000548867	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 27, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17377071, 27506821, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000548867

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 27, 2024)

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

Phenotypic clustering of lamin A/C mutations in neuromuscular patients.

Benedetti S, Menditto I, Degano M, Rodolico C, Merlini L, D'Amico A, Palmucci L, Berardinelli A, Pegoraro E, Trevisan CP, Morandi L, Moroni I, Galluzzi G, Bertini E, Toscano A, Olivè M, Bonne G, Mari F, Caldara R, Fazio R, Mammì I, Carrera P, et al.

Neurology. 2007 Sep 18;69(12):1285-92. Epub 2007 Mar 21.

PubMed [citation]

PMID:: 17377071

Multicenter Experience With Catheter Ablation for Ventricular Tachycardia in Lamin A/C Cardiomyopathy.

Kumar S, Androulakis AF, Sellal JM, Maury P, Gandjbakhch E, Waintraub X, Rollin A, Richard P, Charron P, Baldinger SH, Macintyre CJ, Koplan BA, John RM, Michaud GF, Zeppenfeld K, Sacher F, Lakdawala NK, Stevenson WG, Tedrow UB.

Circ Arrhythm Electrophysiol. 2016 Aug;9(8). doi:pii: e004357. 10.1161/CIRCEP.116.004357.

PubMed [citation]

PMID:: 27506821

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000548867.6

#	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 affects codon 382 of the LMNA mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LMNA protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with cardiomyopathy and conduction disease and/or limb-girdle muscular dystrophy (PMID: 17377071, 27506821; Invitae). ClinVar contains an entry for this variant (Variation ID: 48032). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 20, 2024

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