NM_170707.4(LMNA):c.1862C>T (p.Thr621Met) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 7, 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:: RCV001191647.4

Allele description [Variation Report for NM_170707.4(LMNA):c.1862C>T (p.Thr621Met)]

NM_170707.4(LMNA):c.1862C>T (p.Thr621Met)

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.1862C>T (p.Thr621Met)

HGVS:

NC_000001.11:g.156138651C>T
NG_008692.2:g.61079C>T
NM_001257374.3:c.1526C>T
NM_001282626.2:c.1818+44C>T
NM_170707.4:c.1862C>TMANE SELECT
NM_170708.4:c.1772C>T
NP_001244303.1:p.Thr509Met
NP_733821.1:p.Thr621Met
NP_733822.1:p.Thr591Met
LRG_254t2:c.1862C>T
LRG_254:g.61079C>T
NC_000001.10:g.156108442C>T
NM_170707.2:c.1862C>T
NM_170707.3:c.1862C>T

Protein change:

T509M

Links:

dbSNP: rs765594825

NCBI 1000 Genomes Browser:

rs765594825

Molecular consequence:

NM_001282626.2:c.1818+44C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001257374.3:c.1526C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1862C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1772C>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001359542	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 7, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26383259, 31383942, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001359542

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 7, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Next-generation sequencing of 100 candidate genes in young victims of suspected sudden cardiac death with structural abnormalities of the heart.

Hertz CL, Christiansen SL, Ferrero-Miliani L, Dahl M, Weeke PE; LuCamp., Ottesen GL, Frank-Hansen R, Bundgaard H, Morling N.

Int J Legal Med. 2016 Jan;130(1):91-102. doi: 10.1007/s00414-015-1261-8. Epub 2015 Sep 17.

PubMed [citation]

PMID:: 26383259

A genome-first approach to aggregating rare genetic variants in LMNA for association with electronic health record phenotypes.

Park J, Levin MG, Haggerty CM, Hartzel DN, Judy R, Kember RL, Reza N; Regeneron Genetics Center., Ritchie MD, Owens AT, Damrauer SM, Rader DJ.

Genet Med. 2020 Jan;22(1):102-111. doi: 10.1038/s41436-019-0625-8. Epub 2019 Aug 6.

PubMed [citation]

PMID:: 31383942
PMCID:: PMC7719049

See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001359542.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This missense variant replaces threonine with methionine at codon 621 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy and sudden cardiac death (PMID: 26383259), in an individual affected with cardiomyopathy (PMID: 31383942), and in an individual affected with conduction defect (PMID: 31383942). This variant has been identified in 7/279750 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.

#	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: Sep 29, 2024

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