NM_170707.4(LMNA):c.949G>A (p.Glu317Lys) AND not specified

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 25, 2018
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:: RCV001000784.8

Allele description [Variation Report for NM_170707.4(LMNA):c.949G>A (p.Glu317Lys)]

NM_170707.4(LMNA):c.949G>A (p.Glu317Lys)

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.949G>A (p.Glu317Lys)

HGVS:

NC_000001.11:g.156135913G>A
NG_008692.2:g.58341G>A
NM_001257374.3:c.613G>A
NM_001282624.2:c.706G>A
NM_001282625.2:c.949G>A
NM_001282626.2:c.949G>A
NM_005572.4:c.949G>A
NM_170707.4:c.949G>AMANE SELECT
NM_170708.4:c.949G>A
NP_001244303.1:p.Glu205Lys
NP_001269553.1:p.Glu236Lys
NP_001269554.1:p.Glu317Lys
NP_001269555.1:p.Glu317Lys
NP_005563.1:p.Glu317Lys
NP_733821.1:p.Glu317Lys
NP_733822.1:p.Glu317Lys
LRG_254t2:c.949G>A
LRG_254:g.58341G>A
NC_000001.10:g.156105704G>A
NM_170707.2:c.949G>A
NM_170707.3:c.949G>A
P02545:p.Glu317Lys
c.949G>A

Protein change:

E205K

Links:

UniProtKB: P02545#VAR_039775; dbSNP: rs56816490

NCBI 1000 Genomes Browser:

rs56816490

Molecular consequence:

NM_001257374.3:c.613G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.706G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.949G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.949G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.949G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.949G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.949G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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CNE_RS35790 [Cupriavidus necator N-1]
CNE_RS35790 [Cupriavidus necator N-1]
Gene ID:34312798

Gene
Profile neighbors for GEO Profiles (Select 87927826) (200)
GEO Profiles
Profile neighbors for GEO Profiles (Select 87926842) (200)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 87922317) (19)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001157842	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Likely pathogenic (Sep 25, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001157842

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Likely pathogenic
(Sep 25, 2018)

germline

clinical testing

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001157842.1

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

Description

The LMNA c.949G>A; p.Glu317Lys variant (rs56816490), is reported in the literature in multiple individuals and families affected with dilated cardiomyopathies (DCM) and atrioventricular block with DCM (Arbustini 2002, Millat 2009, Pasotti 2008, Villa 2014, Walsh 2017). This variant is reported as pathogenic/likely pathogenic by multiple laboratories in ClinVar (Variation ID: 48093) and is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The glutamic acid at codon 317 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, the p.Glu317Lys variant is considered to be likely pathogenic. References: Arbustini E et al. Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease. J Am Coll Cardiol. 2002 Mar 20;39(6):981-90. Millat G et al. Validation of high-resolution DNA melting analysis for mutation scanning of the LMNA gene. Clin Biochem. 2009 Jun;42(9):892-8. Pasotti M et al. Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol. 2008 Oct 7;52(15):1250-60. Villa F et al. A G613A missense in the Hutchinson's progeria lamin A/C gene causes a lone, autosomal dominant atrioventricular block. Immun Ageing. 2014 Nov 26;11(1):19. Walsh R et al. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2017 Feb;19(2):192-203.

#	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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