NM_170707.4(LMNA):c.1163G>A (p.Arg388His) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 29, 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:: RCV004018987.1

Allele description [Variation Report for NM_170707.4(LMNA):c.1163G>A (p.Arg388His)]

NM_170707.4(LMNA):c.1163G>A (p.Arg388His)

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.1163G>A (p.Arg388His)

HGVS:

NC_000001.11:g.156136219G>A
NG_008692.2:g.58647G>A
NM_001257374.3:c.827G>A
NM_001282624.2:c.920G>A
NM_001282625.2:c.1163G>A
NM_001282626.2:c.1163G>A
NM_005572.4:c.1163G>A
NM_170707.4:c.1163G>AMANE SELECT
NM_170708.4:c.1163G>A
NP_001244303.1:p.Arg276His
NP_001269553.1:p.Arg307His
NP_001269554.1:p.Arg388His
NP_001269555.1:p.Arg388His
NP_005563.1:p.Arg388His
NP_733821.1:p.Arg388His
NP_733822.1:p.Arg388His
LRG_254t2:c.1163G>A
LRG_254:g.58647G>A
NC_000001.10:g.156106010G>A
NM_170707.2:c.1163G>A
NM_170707.3:c.1163G>A
P02545:p.Arg388His

Protein change:

R276H

Links:

UniProtKB: P02545#VAR_070180; dbSNP: rs267607576

NCBI 1000 Genomes Browser:

rs267607576

Molecular consequence:

NM_001257374.3:c.827G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1163G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1163G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1163G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1163G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1163G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005030786	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 29, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18585512, 20160190, 20590677 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005030786

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 29, 2023)

germline

clinical testing

PubMed (3)
[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

Lamin A/C mutation analysis in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy.

Parks SB, Kushner JD, Nauman D, Burgess D, Ludwigsen S, Peterson A, Li D, Jakobs P, Litt M, Porter CB, Rahko PS, Hershberger RE.

Am Heart J. 2008 Jul;156(1):161-9. doi: 10.1016/j.ahj.2008.01.026. Epub 2008 Mar 12.

PubMed [citation]

PMID:: 18585512
PMCID:: PMC2527054

Morphological analysis of 13 LMNA variants identified in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy.

Cowan J, Li D, Gonzalez-Quintana J, Morales A, Hershberger RE.

Circ Cardiovasc Genet. 2010 Feb;3(1):6-14. doi: 10.1161/CIRCGENETICS.109.905422. Epub 2009 Nov 17.

PubMed [citation]

PMID:: 20160190
PMCID:: PMC2908895

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV005030786.1

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

Description

The p.R388H variant (also known as c.1163G>A), located in coding exon 7 of the LMNA gene, results from a G to A substitution at nucleotide position 1163. The arginine at codon 388 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in a family with dilated cardiomyopathy (DCM); however, it did not segregate with disease in that family and an additional alteration in RBM20 was also identified (Parks SB et al. Am Heart J, 2008 Jul;156:161-9; Li D et al. Clin Transl Sci, 2010 Jun;3:90-7). Additionally, this alteration may impact protein function; however, the physiological relevance of this finding is unclear (Cowan J et al. Circ Cardiovasc Genet, 2010 Feb;3:6-14). This amino acid position is well 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: Sep 29, 2024

ClinVar

Relating variation to medicine