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NM_170707.4(LMNA):c.1718C>T (p.Ser573Leu) AND Cardiomyopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 5, 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:
RCV001188887.4

Allele description [Variation Report for NM_170707.4(LMNA):c.1718C>T (p.Ser573Leu)]

NM_170707.4(LMNA):c.1718C>T (p.Ser573Leu)

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.1718C>T (p.Ser573Leu)
Other names:
chr1-156138507-C-T
HGVS:
  • NC_000001.11:g.156138507C>T
  • NG_008692.2:g.60935C>T
  • NM_001257374.3:c.1382C>T
  • NM_001282626.2:c.1718C>T
  • NM_170707.4:c.1718C>TMANE SELECT
  • NM_170708.4:c.1628C>T
  • NP_001244303.1:p.Ser461Leu
  • NP_001269555.1:p.Ser573Leu
  • NP_733821.1:p.Ser573Leu
  • NP_733822.1:p.Ser543Leu
  • LRG_254t2:c.1718C>T
  • LRG_254:g.60935C>T
  • NC_000001.10:g.156108298C>T
  • NM_170707.2:c.1718C>T
  • NM_170707.3(LMNA):c.1718C>T
  • NM_170707.3:c.1718C>T
  • P02545:p.Ser573Leu
  • c.1718C>T
Protein change:
S461L; SER573LEU
Links:
UniProtKB: P02545#VAR_039789; OMIM: 150330.0041; dbSNP: rs60890628
NCBI 1000 Genomes Browser:
rs60890628
Molecular consequence:
  • NM_001257374.3:c.1382C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282626.2:c.1718C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_170707.4:c.1718C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_170708.4:c.1628C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiomyopathy (CMYO)
Synonyms:
Cardiomyopathies
Identifiers:
MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001356059Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Apr 5, 2023) 		germlineclinical testing

PubMed (15)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.

Taylor MR, Fain PR, Sinagra G, Robinson ML, Robertson AD, Carniel E, Di Lenarda A, Bohlmeyer TJ, Ferguson DA, Brodsky GL, Boucek MM, Lascor J, Moss AC, Li WL, Stetler GL, Muntoni F, Bristow MR, Mestroni L; Familial Dilated Cardiomyopathy Registry Research Group..

J Am Coll Cardiol. 2003 Mar 5;41(5):771-80. Erratum in: J Am Coll Cardiol. 2003 Aug 6;42(3):590.

PubMed [citation]
PMID:
12628721

A homozygous mutation in the lamin A/C gene associated with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features.

Van Esch H, Agarwal AK, Debeer P, Fryns JP, Garg A.

J Clin Endocrinol Metab. 2006 Feb;91(2):517-21. Epub 2005 Nov 8.

PubMed [citation]
PMID:
16278265
See all PubMed Citations (15)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001356059.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (15)

Description

This missense variant replaces serine with leucine at codon 573 of the lamin A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have shown that this variant can restore LMNA protein function in LMNA-deficient fibroblasts (PMID: 16809772), and does not change lamina organization or the interaction with chromatin (Banerjee et al. 2020, https://doi.org/10.1101/2020.05.01.071803). This variant has been reported in individuals affected with dilated cardiomyopathy (PMID: 12628721, 18926329, 28416588, 32616434, 32746448, 35026164), in an individual affected with cardiac arrhythmia (PMID: 28341588), in an individual with a complex phenotype including hypertrophic cardiomyopathy, left ventricular outflow tract obstruction and metabolic syndrome (PMID: 28874324), in an individual affected with Brugada syndrome (PMID: 35026164), and in an individual affected with hypertrophic cardiomyopathy who also carried a pathogenic variant in the MYL2 gene that could explain the observed phenotype (PMID: 32004434). This variant has also been reported in an individual with lipodystrophy (PMID: 17250669), in an individual affected with limb-girdle muscular dystrophy without cardiac involvement (PMID: 17377071), in an individual with progeroid features with no evidence of cardiomyopathy (PMID: 16278265), and in an individual affected with type 2 familial partial lipodystrophy (PMID: 33916827). However, this variant has also been identified in 38/271142 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 20, 2024