NM_170707.4(LMNA):c.1381-1G>A AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 24, 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:: RCV003177759.2

Allele description [Variation Report for NM_170707.4(LMNA):c.1381-1G>A]

NM_170707.4(LMNA):c.1381-1G>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.1381-1G>A

HGVS:

NC_000001.11:g.156136920G>A
NG_008692.2:g.59348G>A
NM_001257374.3:c.1045-1G>A
NM_001282624.2:c.1138-1G>A
NM_001282625.2:c.1381-1G>A
NM_001282626.2:c.1381-1G>A
NM_001406983.1:c.1381-1G>A
NM_001406984.1:c.1381-1G>A
NM_001406985.1:c.1381-1G>A
NM_001406986.1:c.1138-1G>A
NM_001406987.1:c.1138-1G>A
NM_001406988.1:c.1084-1G>A
NM_001406989.1:c.1045-1G>A
NM_001406990.1:c.823-1G>A
NM_001406991.1:c.1381-1G>A
NM_001406992.1:c.1381-1G>A
NM_001406993.1:c.823-1G>A
NM_001406994.1:c.757-1G>A
NM_001406995.1:c.823-1G>A
NM_001406996.1:c.823-1G>A
NM_001406997.1:c.823-1G>A
NM_001406998.1:c.1045-1G>A
NM_001406999.1:c.757-1G>A
NM_001407000.1:c.757-1G>A
NM_001407001.1:c.757-1G>A
NM_001407002.1:c.823-1G>A
NM_001407003.1:c.823-1G>A
NM_005572.4:c.1381-1G>A
NM_170707.4:c.1381-1G>AMANE SELECT
NM_170708.4:c.1381-1G>A
LRG_254t2:c.1381-1G>A
LRG_254:g.59348G>A
NC_000001.10:g.156106711G>A
NM_170707.2:c.1381-1G>A

Molecular consequence:

NM_001257374.3:c.1045-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282624.2:c.1138-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282625.2:c.1381-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282626.2:c.1381-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406983.1:c.1381-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406984.1:c.1381-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406985.1:c.1381-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406986.1:c.1138-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406987.1:c.1138-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406988.1:c.1084-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406989.1:c.1045-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406990.1:c.823-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406991.1:c.1381-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406992.1:c.1381-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406993.1:c.823-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406994.1:c.757-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406995.1:c.823-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406996.1:c.823-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406997.1:c.823-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406998.1:c.1045-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406999.1:c.757-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407000.1:c.757-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407001.1:c.757-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407002.1:c.823-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407003.1:c.823-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_005572.4:c.1381-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_170707.4:c.1381-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_170708.4:c.1381-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003864684	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Feb 24, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003864684

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Feb 24, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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 cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation.

Hasselberg NE, Haland TF, Saberniak J, Brekke PH, Berge KE, Leren TP, Edvardsen T, Haugaa KH.

Eur Heart J. 2018 Mar 7;39(10):853-860. doi: 10.1093/eurheartj/ehx596.

PubMed [citation]

PMID:: 29095976
PMCID:: PMC5939624

Details of each submission

From Ambry Genetics, SCV003864684.2

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

Description

The c.1381-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 8 of the LMNA gene. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort (Hasselberg NE et al. Eur Heart J, 2018 Mar;39:853-860). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely 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: May 1, 2024

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