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NM_170707.4(LMNA):c.949G>A (p.Glu317Lys) AND Primary familial dilated cardiomyopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 2, 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:
RCV001251293.2

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)

Name:
Primary familial dilated cardiomyopathy (FDC)
Synonyms:
Familial dilated cardiomyopathy; Hypokinetic dilated cardiomyopathy, familial
Identifiers:
MONDO: MONDO:0016333; MedGen: C0340427; Orphanet: 217607; OMIM: PS115200

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001426830Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Oct 2, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Clinical and mutational spectrum in a cohort of 105 unrelated patients with dilated cardiomyopathy.

Millat G, Bouvagnet P, Chevalier P, Sebbag L, Dulac A, Dauphin C, Jouk PS, Delrue MA, Thambo JB, Le Metayer P, Seronde MF, Faivre L, Eicher JC, Rousson R.

Eur J Med Genet. 2011 Nov-Dec;54(6):e570-5. doi: 10.1016/j.ejmg.2011.07.005. Epub 2011 Aug 4.

PubMed [citation]
PMID:
21846512

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]
PMID:
27532257
PMCID:
PMC5116235
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001426830.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: LMNA c.949G>A (p.Glu317Lys) results in a conservative amino acid change located in the Intermediate filament, rod domain (IPR039008) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248396 control chromosomes (gnomAD). c.949G>A has been reported in the literature in multiple individuals and families affected with Dilated Cardiomyopathy (DCM) or DCM and atrioventricular block (AVB) or AVB alone; co-segregation with disease was documented within different families (e.g. Arbustini_2002, Pasotti_2008, Millat_2011, Villa_2014, Walsh_2017). The following publications have been ascertained in the context of this evaluation (PMID: 11897440, 21846512, 18926329, 25469153, 27532257). Nine submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024