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

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 8, 2021
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:
RCV000620488.4

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]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000737036Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Mar 8, 2021) 		germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot 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 landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]
PMID:
24503780
See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV000737036.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

The c.1146C>T variant (also known as p.G382G), located in coding exon 6, results from a C to T substitution at nucleotide position 1146 of the LMNA gene. This nucleotide substitution does not change the amino acid at codon 382. This alteration has been reported in individuals with limb-girdle muscular dystrophy, dilated cardiomyopathy (DCM), and cardiac conduction disease (Benedetti S et al. Neurology, 2007 Sep;69:1285-92; Di Resta C et al. Clin. Chim. Acta, 2014 Sep;436:276-82). This alteration was also reported in DCM and left ventricular non-compaction cohorts, but clinical details were limited and some patients had additional variants in other cardiac-related genes (Pugh TJ et al. Genet. Med., 2014 Aug;16:601-8; Miszalski-Jamka K et al. Circ Cardiovasc Genet, 2017 Aug;10:[Epub ahead of print]). This nucleotide position is not well conserved in available vertebrate species, and threonine is the reference nucleotide in other vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. Published RNA studies have demonstrated this alteration leads to the creation of a new splice donor site, which leads to deletion of the last 13 nucleotides of exon 6, causing a frameshift that introduces a premature stop codon (Benedetti S et al. Neurology, 2007 Sep;69:1285-92; Di Resta C et al. Clin. Chim. Acta, 2014 Sep;436:276-82). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Jul 15, 2024