NM_170707.4(LMNA):c.1184C>G (p.Ser395Trp) AND Primary dilated cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 26, 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:: RCV004016329.2

Allele description [Variation Report for NM_170707.4(LMNA):c.1184C>G (p.Ser395Trp)]

NM_170707.4(LMNA):c.1184C>G (p.Ser395Trp)

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.1184C>G (p.Ser395Trp)

HGVS:

NC_000001.11:g.156136240C>G
NG_008692.2:g.58668C>G
NM_001257374.3:c.848C>G
NM_001282624.2:c.941C>G
NM_001282625.2:c.1184C>G
NM_001282626.2:c.1184C>G
NM_001406983.1:c.1184C>G
NM_001406984.1:c.1184C>G
NM_001406985.1:c.1184C>G
NM_001406986.1:c.941C>G
NM_001406987.1:c.941C>G
NM_001406988.1:c.887C>G
NM_001406989.1:c.848C>G
NM_001406990.1:c.626C>G
NM_001406991.1:c.1184C>G
NM_001406992.1:c.1184C>G
NM_001406993.1:c.626C>G
NM_001406994.1:c.560C>G
NM_001406995.1:c.626C>G
NM_001406996.1:c.626C>G
NM_001406997.1:c.626C>G
NM_001406998.1:c.848C>G
NM_001406999.1:c.560C>G
NM_001407000.1:c.560C>G
NM_001407001.1:c.560C>G
NM_001407002.1:c.626C>G
NM_001407003.1:c.626C>G
NM_005572.4:c.1184C>G
NM_170707.4:c.1184C>GMANE SELECT
NM_170708.4:c.1184C>G
NP_001244303.1:p.Ser283Trp
NP_001269553.1:p.Ser314Trp
NP_001269554.1:p.Ser395Trp
NP_001269555.1:p.Ser395Trp
NP_001393912.1:p.Ser395Trp
NP_001393913.1:p.Ser395Trp
NP_001393914.1:p.Ser395Trp
NP_001393915.1:p.Ser314Trp
NP_001393916.1:p.Ser314Trp
NP_001393917.1:p.Ser296Trp
NP_001393918.1:p.Ser283Trp
NP_001393919.1:p.Ser209Trp
NP_001393920.1:p.Ser395Trp
NP_001393921.1:p.Ser395Trp
NP_001393922.1:p.Ser209Trp
NP_001393923.1:p.Ser187Trp
NP_001393924.1:p.Ser209Trp
NP_001393925.1:p.Ser209Trp
NP_001393926.1:p.Ser209Trp
NP_001393927.1:p.Ser283Trp
NP_001393928.1:p.Ser187Trp
NP_001393929.1:p.Ser187Trp
NP_001393930.1:p.Ser187Trp
NP_001393931.1:p.Ser209Trp
NP_001393932.1:p.Ser209Trp
NP_005563.1:p.Ser395Trp
NP_005563.1:p.Ser395Trp
NP_733821.1:p.Ser395Trp
NP_733821.1:p.Ser395Trp
NP_733822.1:p.Ser395Trp
NP_733822.1:p.Ser395Trp
LRG_254t1:c.1184C>G
LRG_254t2:c.1184C>G
LRG_254t3:c.1184C>G
LRG_254:g.58668C>G
LRG_254p1:p.Ser395Trp
LRG_254p2:p.Ser395Trp
LRG_254p3:p.Ser395Trp
NC_000001.10:g.156106031C>G
NM_005572.3:c.1184C>G
NM_170707.2:c.1184C>G
NM_170708.2:c.1184C>G
NR_047544.1:n.1825C>G
NR_047545.1:n.1072C>G

Protein change:

S187W

Molecular consequence:

NM_001257374.3:c.848C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.941C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1184C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1184C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406983.1:c.1184C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406984.1:c.1184C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406985.1:c.1184C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406986.1:c.941C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406987.1:c.941C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406988.1:c.887C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406989.1:c.848C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406990.1:c.626C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406991.1:c.1184C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406992.1:c.1184C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406993.1:c.626C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406994.1:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406995.1:c.626C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406996.1:c.626C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406997.1:c.626C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406998.1:c.848C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406999.1:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407000.1:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407001.1:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407002.1:c.626C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407003.1:c.626C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1184C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1184C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1184C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Primary dilated cardiomyopathy (DCM)
Synonyms:: Dilated Cardiomyopathy
Identifiers:: EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004831012	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Jun 26, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004831012

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Jun 26, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

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 All of Us Research Program, National Institutes of Health, SCV004831012.1

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

Description

This missense variant replaces serine with tryptophan at codon 395 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 not been reported in individuals affected with LMNA-related disorders in the literature. This variant has not been identified 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	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 7, 2024

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