NM_170707.4(LMNA):c.763del (p.Gln255fs) AND Primary dilated cardiomyopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 4, 2012
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:: RCV000041364.5

Allele description [Variation Report for NM_170707.4(LMNA):c.763del (p.Gln255fs)]

NM_170707.4(LMNA):c.763del (p.Gln255fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_170707.4(LMNA):c.763del (p.Gln255fs)

HGVS:

NC_000001.10:g.156104718del
NC_000001.11:g.156134928del
NG_008692.2:g.57356del
NM_001257374.3:c.427del
NM_001282624.2:c.520del
NM_001282625.2:c.763del
NM_001282626.2:c.763del
NM_005572.4:c.763del
NM_170707.4:c.763delMANE SELECT
NM_170708.4:c.763del
NP_001244303.1:p.Gln143fs
NP_001269553.1:p.Gln174fs
NP_001269554.1:p.Gln255fs
NP_001269555.1:p.Gln255fs
NP_005563.1:p.Gln255fs
NP_733821.1:p.Gln255fs
NP_733822.1:p.Gln255fs
LRG_254t2:c.763del
LRG_254:g.57356del
NC_000001.10:g.156104718del
NC_000001.10:g.156104719del
NC_000001.10:g.156104719delC
NM_170707.2:c.763delC
c.763delC
p.Gln255ArgfsX225

Protein change:

Q143fs

Links:

dbSNP: rs397517908

NCBI 1000 Genomes Browser:

rs397517908

Molecular consequence:

NM_001257374.3:c.427del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282624.2:c.520del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282625.2:c.763del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282626.2:c.763del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005572.4:c.763del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_170707.4:c.763del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_170708.4:c.763del - 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
SCV000065057	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Dec 4, 2012)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000065057

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Dec 4, 2012)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000065057.5

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

Description

The Gln255fs variant in LMNA has not been reported but has been identified in on e individual with reduced ejection fraction (this individual's brother) previous ly tested by our laboratory. This frameshift variant is predicted to alter the p rotein?s amino acid sequence beginning at position 255 and lead to a premature t ermination codon 225 amino acids downstream. This alteration is then predicted t o lead to a truncated or absent protein. Heterozygous loss of function of functi on of the LMNA gene is an established disease mechanism in DCM patients. In summ ary, the Gln255fs variant is likely to be pathogenic.

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

Last Updated: Apr 6, 2024

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