NM_170707.4(LMNA):c.1279C>T (p.Arg427Cys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 27, 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:: RCV003479048.1

Allele description [Variation Report for NM_170707.4(LMNA):c.1279C>T (p.Arg427Cys)]

NM_170707.4(LMNA):c.1279C>T (p.Arg427Cys)

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.1279C>T (p.Arg427Cys)

Other names:

p.R427C:CGC>TGC

HGVS:

NC_000001.11:g.156136335C>T
NG_008692.2:g.58763C>T
NM_001257374.3:c.943C>T
NM_001282624.2:c.1036C>T
NM_001282625.2:c.1279C>T
NM_001282626.2:c.1279C>T
NM_005572.4:c.1279C>T
NM_170707.4:c.1279C>TMANE SELECT
NM_170708.4:c.1279C>T
NP_001244303.1:p.Arg315Cys
NP_001269553.1:p.Arg346Cys
NP_001269554.1:p.Arg427Cys
NP_001269555.1:p.Arg427Cys
NP_005563.1:p.Arg427Cys
NP_733821.1:p.Arg427Cys
NP_733822.1:p.Arg427Cys
LRG_254t2:c.1279C>T
LRG_254:g.58763C>T
NC_000001.10:g.156106126C>T
NM_170707.2:c.1279C>T
NM_170707.3:c.1279C>T

Protein change:

R315C

Links:

dbSNP: rs373584456

NCBI 1000 Genomes Browser:

rs373584456

Molecular consequence:

NM_001257374.3:c.943C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.1036C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1279C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1279C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1279C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1279C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1279C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004223206	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Nov 27, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 28663758, 29773157, 28082330, 31383942, 35449878, 36267857, 36646731, 35772917 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004223206

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Nov 27, 2023)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

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

Citations

PubMed

LMNA Sequences of 60,706 Unrelated Individuals Reveal 132 Novel Missense Variants in A-Type Lamins and Suggest a Link between Variant p.G602S and Type 2 Diabetes.

Florwick A, Dharmaraj T, Jurgens J, Valle D, Wilson KL.

Front Genet. 2017;8:79. doi: 10.3389/fgene.2017.00079.

PubMed [citation]

PMID:: 28663758
PMCID:: PMC5471320

Genetic Etiology for Alcohol-Induced Cardiac Toxicity.

Ware JS, Amor-Salamanca A, Tayal U, Govind R, Serrano I, Salazar-Mendiguchía J, García-Pinilla JM, Pascual-Figal DA, Nuñez J, Guzzo-Merello G, Gonzalez-Vioque E, Bardaji A, Manito N, López-Garrido MA, Padron-Barthe L, Edwards E, Whiffin N, Walsh R, Buchan RJ, Midwinter W, Wilk A, Prasad S, et al.

J Am Coll Cardiol. 2018 May 22;71(20):2293-2302. doi: 10.1016/j.jacc.2018.03.462.

PubMed [citation]

PMID:: 29773157
PMCID:: PMC5957753

See all PubMed Citations (8)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004223206.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

Variant summary: LMNA c.1279C>T (p.Arg427Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251684 control chromosomes (gnomAD and publication data). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1279C>T has been reported in the literature in individuals affected with hypertrophic cardiomyopathy, sudden unexpected death in infants, atrioventricular and left bundle branch block, chronic kidney disease or steroid-sensitive nephrotic syndrome (Walsh_2017, Park_2019, Heathfield_2021, Pessente_2022, Isaranuwatchai_2022). These reports do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28663758, 36267857, 36646731, 35772917, 31383942, 35449878, 28082330, 29773157). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: May 7, 2024

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