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NM_170707.4(LMNA):c.1146C>T (p.Gly382=) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 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:
RCV000041309.8

Allele description [Variation Report for NM_170707.4(LMNA):c.1146C>T (p.Gly382=)]

NM_170707.4(LMNA):c.1146C>T (p.Gly382=)

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.1146C>T (p.Gly382=)
Other names:
p.G382G:GGC>GGT
HGVS:
  • NC_000001.11:g.156136110C>T
  • NG_008692.2:g.58538C>T
  • NM_001257374.3:c.810C>T
  • NM_001282624.2:c.903C>T
  • NM_001282625.2:c.1146C>T
  • NM_001282626.2:c.1146C>T
  • NM_005572.4:c.1146C>T
  • NM_170707.4:c.1146C>TMANE SELECT
  • NM_170708.4:c.1146C>T
  • NP_001244303.1:p.Gly270=
  • NP_001269553.1:p.Gly301=
  • NP_001269554.1:p.Gly382=
  • NP_001269555.1:p.Gly382=
  • NP_005563.1:p.Gly382=
  • NP_733821.1:p.Gly382=
  • NP_733822.1:p.Gly382=
  • LRG_254t2:c.1146C>T
  • LRG_254:g.58538C>T
  • NC_000001.10:g.156105901C>T
  • NM_170707.2:c.1146C>T
  • NM_170707.3:c.1146C>T
  • c.1146C>T
Links:
dbSNP: rs57508089
NCBI 1000 Genomes Browser:
rs57508089
Molecular consequence:
  • NM_001257374.3:c.810C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001282624.2:c.903C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001282625.2:c.1146C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001282626.2:c.1146C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_005572.4:c.1146C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_170707.4:c.1146C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_170708.4:c.1146C>T - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
3

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
Name:
Neuromuscular disease
Synonyms:
Neuromuscular Diseases; Neuromuscular disorder; Neuromyopathy
Identifiers:
MONDO: MONDO:0019056; MeSH: D009468; MedGen: C0027868

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000065001Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(May 25, 2018) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided73not 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

Evaluation of damaging effects of splicing mutations: validation of an in vitro method for diagnostic laboratories.

Di Resta C, Manzoni M, Berisso MZ, Siciliano G, Benedetti S, Ferrari M.

Clin Chim Acta. 2014 Sep 25;436:276-82. doi: 10.1016/j.cca.2014.05.026. Epub 2014 Jun 7.

PubMed [citation]
PMID:
24915601
See all PubMed Citations (5)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000065001.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided7not providednot providedclinical testing PubMed (5)

Description

The p.Gly382Gly variant in LMNA has been previously reported in 1 individual wit h LVNC, 2 individuals with DCM and conduction system disease, and 1 individual w ith childhood-onset limb-girdle muscular dystrophy and adult-onset DCM with SVT (Benedetti 2007, Di Resta 2014, Ito 2017, Miszalski-Jamka 2017, LMM Data). It al so segregated with DCM in 2 affected relative. This variant has also been report ed by other clinical laboratories in ClinVar (Variation ID: 48032). This variant was absent from large population studies. This variant does not alter the amino acid residue, but RNA studies showed that it creates a new splice site in the 3 ' end of exon 6 resulting in the deletion of the remaining 13 bases in this exon (Benedetti 2007, Di Resta 2014). This deletion causes a frameshift, altering th e protein's amino acid sequence beginning at codon 383 and leading to a prematur e stop codon 93 amino acids downstream, which is predicted to lead to a truncate d or absent protein. In summary, although additional studies are required to ful ly establish its clinical significance, the p.Gly382Gly variant is likely pathog enic. ACMG/AMP criteria applied: PS3, PM2, PS4_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided7not provided3not provided

Last Updated: Oct 20, 2024