NM_170707.4(LMNA):c.659G>A (p.Arg220His) AND Primary dilated cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 10, 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:: RCV004000123.2

Allele description [Variation Report for NM_170707.4(LMNA):c.659G>A (p.Arg220His)]

NM_170707.4(LMNA):c.659G>A (p.Arg220His)

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.659G>A (p.Arg220His)

HGVS:

NC_000001.11:g.156134824G>A
NG_008692.2:g.57252G>A
NM_001257374.3:c.323G>A
NM_001282624.2:c.416G>A
NM_001282625.2:c.659G>A
NM_001282626.2:c.659G>A
NM_005572.4:c.659G>A
NM_170707.4:c.659G>AMANE SELECT
NM_170708.4:c.659G>A
NP_001244303.1:p.Arg108His
NP_001269553.1:p.Arg139His
NP_001269554.1:p.Arg220His
NP_001269555.1:p.Arg220His
NP_005563.1:p.Arg220His
NP_733821.1:p.Arg220His
NP_733822.1:p.Arg220His
LRG_254t2:c.659G>A
LRG_254:g.57252G>A
NC_000001.10:g.156104615G>A
NM_170707.2:c.659G>A
NM_170707.3:c.659G>A

Protein change:

R108H

Links:

dbSNP: rs780066296

NCBI 1000 Genomes Browser:

rs780066296

Molecular consequence:

NM_001257374.3:c.323G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.416G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.659G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.659G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.659G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.659G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.659G>A - 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
SCV004846744	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Jul 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32789750, 35284542, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004846744

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Jul 10, 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	2	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Novel variants in women with premature ovarian function decline identified via whole-exome sequencing.

Tang R, Yu Q.

J Assist Reprod Genet. 2020 Oct;37(10):2487-2502. doi: 10.1007/s10815-020-01919-y. Epub 2020 Aug 13.

PubMed [citation]

PMID:: 32789750
PMCID:: PMC7550486

Genetic variants in Chinese patients with sporadic dilated cardiomyopathy: a cross-sectional study.

Shen C, Xu L, Sun X, Sun A, Ge J.

Ann Transl Med. 2022 Feb;10(3):129. doi: 10.21037/atm-21-6774.

PubMed [citation]

PMID:: 35284542
PMCID:: PMC8904992

See all PubMed Citations (3)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004846744.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (3)

Description

This missense variant replaces arginine with histidine at codon 220 of the lamin A/C proteins. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with dilated cardiomyopathy (PMID: 35284542; Garcia-Pavia et al. 2013, doi: 10.1093/eurheartj/eht309.P4234). It has also been reported in an individual affected with secondary amenorrhea (PMID: 32789750). This variant has been identified in 4/251376 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	108544	not provided	not provided		2	not provided	not provided	not provided

Last Updated: May 7, 2024

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