NM_170707.4(LMNA):c.1390A>G (p.Met464Val) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 8, 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:: RCV000772026.3

Allele description [Variation Report for NM_170707.4(LMNA):c.1390A>G (p.Met464Val)]

NM_170707.4(LMNA):c.1390A>G (p.Met464Val)

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.1390A>G (p.Met464Val)

HGVS:

NC_000001.11:g.156136930A>G
NG_008692.2:g.59358A>G
NM_001257374.3:c.1054A>G
NM_001282624.2:c.1147A>G
NM_001282625.2:c.1390A>G
NM_001282626.2:c.1390A>G
NM_005572.4:c.1390A>G
NM_170707.4:c.1390A>GMANE SELECT
NM_170708.4:c.1390A>G
NP_001244303.1:p.Met352Val
NP_001269553.1:p.Met383Val
NP_001269554.1:p.Met464Val
NP_001269555.1:p.Met464Val
NP_005563.1:p.Met464Val
NP_733821.1:p.Met464Val
NP_733822.1:p.Met464Val
LRG_254t2:c.1390A>G
LRG_254:g.59358A>G
NC_000001.10:g.156106721A>G
NM_170707.2:c.1390A>G
NM_170707.3:c.1390A>G

Protein change:

M352V

Links:

dbSNP: rs200262654

NCBI 1000 Genomes Browser:

rs200262654

Molecular consequence:

NM_001257374.3:c.1054A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.1147A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1390A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1390A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1390A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1390A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1390A>G - 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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Homo sapiens inhibitor of growth family, member 3, mRNA (cDNA clone IMAGE:7939534), complete cds
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000904982	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 8, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31383942, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000904982

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 8, 2023)

germline

clinical testing

PubMed (2)
[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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000904982.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces methionine with valine at codon 464 of the LMNA protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with cardiomyopathy and conduction defect (PMID: 31383942). This variant has been identified in 7/282082 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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