NM_170707.4(LMNA):c.1324G>A (p.Val442Met) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 6, 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:: RCV000621062.4

Allele description [Variation Report for NM_170707.4(LMNA):c.1324G>A (p.Val442Met)]

NM_170707.4(LMNA):c.1324G>A (p.Val442Met)

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.1324G>A (p.Val442Met)

Other names:

p.Val442Met

HGVS:

NC_000001.11:g.156136380G>A
NG_008692.2:g.58808G>A
NM_001257374.3:c.988G>A
NM_001282624.2:c.1081G>A
NM_001282625.2:c.1324G>A
NM_001282626.2:c.1324G>A
NM_005572.4:c.1324G>A
NM_170707.4:c.1324G>AMANE SELECT
NM_170708.4:c.1324G>A
NP_001244303.1:p.Val330Met
NP_001269553.1:p.Val361Met
NP_001269554.1:p.Val442Met
NP_001269555.1:p.Val442Met
NP_005563.1:p.Val442Met
NP_005563.1:p.Val442Met
NP_733821.1:p.Val442Met
NP_733822.1:p.Val442Met
LRG_254t1:c.1324G>A
LRG_254t2:c.1324G>A
LRG_254:g.58808G>A
LRG_254p1:p.Val442Met
NC_000001.10:g.156106171G>A
NM_001257374.3:c.988G>A
NM_005572.3:c.1324G>A
NM_170707.2:c.1324G>A
NM_170707.3:c.1324G>A

Protein change:

V330M

Links:

dbSNP: rs368542816

NCBI 1000 Genomes Browser:

rs368542816

Molecular consequence:

NM_001257374.3:c.988G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.1081G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1324G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1324G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1324G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1324G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1324G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000736893	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28663758, 31383942 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000736893

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 6, 2023)

germline

clinical testing

PubMed (2)
[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

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

Details of each submission

From Ambry Genetics, SCV000736893.6

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

Description

The p.V442M variant (also known as c.1324G>A), located in coding exon 7 of the LMNA gene, results from a G to A substitution at nucleotide position 1324. The valine at codon 442 is replaced by methionine, an amino acid with highly similar properties, and is located in the Ig-fold domain. This amino acid position is highly 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.

#	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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