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NM_170707.4(LMNA):c.1201C>T (p.Arg401Cys) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 28, 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:
RCV002345327.3

Allele description [Variation Report for NM_170707.4(LMNA):c.1201C>T (p.Arg401Cys)]

NM_170707.4(LMNA):c.1201C>T (p.Arg401Cys)

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.1201C>T (p.Arg401Cys)
HGVS:
  • NC_000001.11:g.156136257C>T
  • NG_008692.2:g.58685C>T
  • NM_001257374.3:c.865C>T
  • NM_001282624.2:c.958C>T
  • NM_001282625.2:c.1201C>T
  • NM_001282626.2:c.1201C>T
  • NM_005572.4:c.1201C>T
  • NM_170707.4:c.1201C>TMANE SELECT
  • NM_170708.4:c.1201C>T
  • NP_001244303.1:p.Arg289Cys
  • NP_001269553.1:p.Arg320Cys
  • NP_001269554.1:p.Arg401Cys
  • NP_001269555.1:p.Arg401Cys
  • NP_005563.1:p.Arg401Cys
  • NP_005563.1:p.Arg401Cys
  • NP_733821.1:p.Arg401Cys
  • NP_733822.1:p.Arg401Cys
  • LRG_254t1:c.1201C>T
  • LRG_254t2:c.1201C>T
  • LRG_254:g.58685C>T
  • LRG_254p1:p.Arg401Cys
  • NC_000001.10:g.156106048C>T
  • NM_005572.3:c.1201C>T
  • NM_170707.2:c.1201C>T
  • NM_170707.3:c.1201C>T
  • P02545:p.Arg401Cys
  • c.1201C>T
Protein change:
R289C
Links:
UniProtKB: P02545#VAR_072818; dbSNP: rs61094188
NCBI 1000 Genomes Browser:
rs61094188
Molecular consequence:
  • NM_001257374.3:c.865C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282624.2:c.958C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282625.2:c.1201C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282626.2:c.1201C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005572.4:c.1201C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_170707.4:c.1201C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_170708.4:c.1201C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002653838Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Dec 28, 2023) 		germlineclinical testing

PubMed (19)
[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

[Hauptmann-Thannhauser muscular dystrophy and differential diagnosis of myopathies associated with contractures].

Hanisch F, Neudecker S, Wehnert M, Zierz S.

Nervenarzt. 2002 Oct;73(10):1004-11. German.

PubMed [citation]
PMID:
12376891

Frequent low penetrance mutations in the Lamin A/C gene, causing Emery Dreifuss muscular dystrophy.

Vytopil M, Ricci E, Dello Russo A, Hanisch F, Neudecker S, Zierz S, Ricotti R, Demay L, Richard P, Wehnert M, Bonne G, Merlini L, Toniolo D.

Neuromuscul Disord. 2002 Dec;12(10):958-63.

PubMed [citation]
PMID:
12467752
See all PubMed Citations (19)

Details of each submission

From Ambry Genetics, SCV002653838.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (19)

Description

The p.R401C variant (also known as c.1201C>T), located in coding exon 7 of the LMNA gene, results from a C to T substitution at nucleotide position 1201. The arginine at codon 401 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was originally reported in an individual with skeletal, muscular, and cardiac findings, as well as in his unaffected mother and sister (Hanisch F et al. Nervenarzt, 2002 Oct;73:1004-11; Vytopil M et al. Neuromuscul. Disord., 2002 Dec;12:958-63). This variant has also been detected in individuals with Emery-Dreifuss muscular dystrophy, including one case of a compound heterozygote who also had an LMNA truncating variant (Muchir A et al. Muscle Nerve, 2004 Oct;30:444-50; Emerson LJ et al. Biochim. Biophys. Acta, 2009 Aug;1792:810-21). In addition, this variant has been described in individuals and genetic testing cohorts with dilated cardiomyopathy, including two affected siblings, but clinical details were limited (Pugh TJ et al. Genet. Med., 2014 Aug;16:601-8; Chami N et al. Can J Cardiol, 2014 Dec;30:1655-61; Walsh R et al. Genet. Med., 2017 02;19:192-203; Verdonschot JAJ et al. Circ Genom Precis Med, 2020 10;13:476-487). Finally, this variant was reported as maternally inherited in a left ventricular non-compaction (LVNC) case with a maternal family history of atrial fibrillation and sudden cardiac death, but whose carrier mother was apparently unaffected (Baban A et al. Front Pediatr, 2020 Jul;8:374). Functional studies have suggested this alteration may impact protein function; however, the clinical relevance of those results is unclear (Muchir A et al. Muscle Nerve, 2004 Oct;30:444-50; Capanni C et al. Exp. Cell Res., 2003 Nov;291:122-34; Yang L et al. PLoS ONE, 2013 Aug;8:e71850; Angori S et al. Cell. Physiol. Biochem., 2017 May;42:169-184). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Oct 8, 2024