NM_170707.4(LMNA):c.522del (p.Ala175fs) AND Primary dilated cardiomyopathy

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:: RCV003996717.2

Allele description [Variation Report for NM_170707.4(LMNA):c.522del (p.Ala175fs)]

NM_170707.4(LMNA):c.522del (p.Ala175fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_170707.4(LMNA):c.522del (p.Ala175fs)

HGVS:

NC_000001.11:g.156134411del
NG_008692.2:g.56839del
NM_001257374.3:c.186del
NM_001282624.2:c.279del
NM_001282625.2:c.522del
NM_001282626.2:c.522del
NM_005572.4:c.522del
NM_170707.4:c.522delMANE SELECT
NM_170708.4:c.522del
NP_001244303.1:p.Ala63fs
NP_001269553.1:p.Ala94fs
NP_001269554.1:p.Ala175fs
NP_001269555.1:p.Ala175fs
NP_005563.1:p.Ala175fs
NP_733821.1:p.Ala175fs
NP_733822.1:p.Ala175fs
LRG_254t2:c.522del
LRG_254:g.56839del
NC_000001.10:g.156104202del
NM_170707.2:c.522del
NM_170707.2:c.522delA
p.A175PfsX2

Protein change:

A175fs

Links:

dbSNP: rs794728606

NCBI 1000 Genomes Browser:

rs794728606

Molecular consequence:

NM_001257374.3:c.186del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282624.2:c.279del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282625.2:c.522del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282626.2:c.522del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005572.4:c.522del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_170707.4:c.522del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_170708.4:c.522del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Primary dilated cardiomyopathy (DCM)
Synonyms:: Dilated Cardiomyopathy
Identifiers:: EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004830219	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 8, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17377071, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004830219

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 8, 2023)

germline

clinical testing

PubMed (2)
[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	1	not provided	not provided	108544	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004830219.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

This variant deletes 1 nucleotide in exon 3 of the LMNA gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been reported in an individual affected with cardiomyopathy and limb-girdle muscular dystrophy (PMID: 17377071). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of LMNA function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jul 23, 2024

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