NM_170707.4(LMNA):c.356+1G>A AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 19, 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:: RCV000689313.8

Allele description [Variation Report for NM_170707.4(LMNA):c.356+1G>A]

NM_170707.4(LMNA):c.356+1G>A

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.356+1G>A

HGVS:

NC_000001.11:g.156115275G>A
NG_008692.2:g.37703G>A
NM_001282625.2:c.356+1G>A
NM_001282626.2:c.356+1G>A
NM_001406983.1:c.356+1G>A
NM_001406984.1:c.356+1G>A
NM_001406985.1:c.356+1G>A
NM_001406986.1:c.-68+1G>A
NM_001406990.1:c.-46+1G>A
NM_001406991.1:c.356+1G>A
NM_001406992.1:c.356+1G>A
NM_001406993.1:c.-203+8452G>A
NM_001406994.1:c.-309+1G>A
NM_001406995.1:c.-46+1G>A
NM_001406999.1:c.-489+1G>A
NM_001407000.1:c.-309+1G>A
NM_001407001.1:c.-152+1G>A
NM_001407002.1:c.-46+1G>A
NM_001407003.1:c.-203+8452G>A
NM_005572.4:c.356+1G>A
NM_170707.4:c.356+1G>AMANE SELECT
NM_170708.4:c.356+1G>A
LRG_254t2:c.356+1G>A
LRG_254:g.37703G>A
NC_000001.10:g.156085066G>A
NM_170707.2:c.356+1G>A
NM_170707.3:c.356+1G>A

Links:

dbSNP: rs794728589

NCBI 1000 Genomes Browser:

rs794728589

Molecular consequence:

NM_001406993.1:c.-203+8452G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001407003.1:c.-203+8452G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001282625.2:c.356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001282626.2:c.356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406983.1:c.356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406984.1:c.356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406985.1:c.356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406986.1:c.-68+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406990.1:c.-46+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406991.1:c.356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406992.1:c.356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406994.1:c.-309+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406995.1:c.-46+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406999.1:c.-489+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407000.1:c.-309+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407001.1:c.-152+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407002.1:c.-46+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_005572.4:c.356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_170707.4:c.356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_170708.4:c.356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000816956	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 19, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23062543, 16199547, 18585512, 18926329, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000816956

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 19, 2020)

germline

clinical testing

PubMed (5)
[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

Quantitative expression of the mutated lamin A/C gene in patients with cardiolaminopathy.

Narula N, Favalli V, Tarantino P, Grasso M, Pilotto A, Bellazzi R, Serio A, Gambarin FI, Charron P, Meder B, Pinto Y, Elliott PM, Mogensen J, Bolognesi M, Bollati M, Arbustini E.

J Am Coll Cardiol. 2012 Nov 6;60(19):1916-20. doi: 10.1016/j.jacc.2012.05.059. Epub 2012 Oct 10.

PubMed [citation]

PMID:: 23062543

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000816956.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Disruption of this splice site has been observed in individuals with clinical features of LMNA-related conditions (PMID: 23062543, Invitae). ClinVar contains an entry for this variant (Variation ID: 200933). For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LMNA are known to be pathogenic (PMID: 18585512, 18926329). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 1 of the LMNA gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	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: Feb 20, 2024

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