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NM_170707.3(LMNA):c.992G>A (p.Arg331Gln) AND Primary dilated cardiomyopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 19, 2013
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:
RCV000041384.2

Allele description

NM_170707.3(LMNA):c.992G>A (p.Arg331Gln)

Gene:
LMNA:lamin A/C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q22
Genomic location:
Preferred name:
NM_170707.3(LMNA):c.992G>A (p.Arg331Gln)
Other names:
p.R331Q:CGG>CAG
HGVS:
  • NC_000001.11:g.156135956G>A
  • NG_008692.2:g.58384G>A
  • NM_005572.3:c.992G>A
  • NM_170707.3:c.992G>A
  • NM_170708.3:c.992G>A
  • NP_005563.1:p.Arg331Gln
  • NP_733821.1:p.Arg331Gln
  • NP_733822.1:p.Arg331Gln
  • LRG_254t1:c.992G>A
  • LRG_254:g.58384G>A
  • LRG_254p1:p.Arg331Gln
  • LRG_254p2:p.Arg331Gln
  • LRG_254p3:p.Arg331Gln
  • NC_000001.10:g.156105747G>A
  • NM_170707.2:c.992G>A
  • c.992G>A
Protein change:
R331Q
Links:
dbSNP: rs59301204
NCBI 1000 Genomes Browser:
rs59301204
Allele Frequency:
0.00002(A)
Molecular consequence:
  • NM_170707.3:c.992G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Primary dilated cardiomyopathy (DCM)
Synonyms:
Congestive cardiomyopathy
Identifiers:
EFO: EFO_0000407; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000065077Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(Mar 19, 2013) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided31not providednot providednot providedclinical 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

The role of Lamin A/C mutations in Danish patients with idiopathic dilated cardiomyopathy.

Møller DV, Pham TT, Gustafsson F, Hedley P, Ersbøll MK, Bundgaard H, Andersen CB, Torp-Pedersen C, Køber L, Christiansen M.

Eur J Heart Fail. 2009 Nov;11(11):1031-5. doi: 10.1093/eurjhf/hfp134. No abstract available.

PubMed [citation]
PMID:
19875404
See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000065077.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (3)

Description

The Arg331Gln variant in LMNA has been reported in 2 individuals with DCM and arrhythmias and was absent from at least 700 control chromosomes (Benedetti 2007, Møller 2009). This variant has been identified in 1 family tested by our laboratory in cis with another disease-causing LMNA variant (Arg541Cys; LMM unpublished data). Arginine (Arg) at position 331 is highly conserved evolution and another likely disease-causing variant (Arg331Pro; dbSNP rs59301204) has been reported at the same position (Benedetti 2007). Additional computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) are uninformative. In summary, the strong clinical correlation, absence from controls, and presence of another variant at the same position, all support that the Arg331Gln variant is likely to be pathogenic when seen in isolation. However, additional studies are still required to fully establish its clinical significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided3not provided1not provided

Last Updated: Apr 2, 2018