NM_170707.4(LMNA):c.1580G>A (p.Arg527His) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Dec 16, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000057326.16

Allele description [Variation Report for NM_170707.4(LMNA):c.1580G>A (p.Arg527His)]

NM_170707.4(LMNA):c.1580G>A (p.Arg527His)

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.1580G>A (p.Arg527His)

Other names:

p.R527H:CGT>CAT

HGVS:

NC_000001.11:g.156137204G>A
NG_008692.2:g.59632G>A
NM_001257374.3:c.1244G>A
NM_001282624.2:c.1337G>A
NM_001282625.2:c.1580G>A
NM_001282626.2:c.1580G>A
NM_005572.4:c.1580G>A
NM_170707.4:c.1580G>AMANE SELECT
NM_170708.4:c.1580G>A
NP_001244303.1:p.Arg415His
NP_001269553.1:p.Arg446His
NP_001269554.1:p.Arg527His
NP_001269555.1:p.Arg527His
NP_005563.1:p.Arg527His
NP_005563.1:p.Arg527His
NP_733821.1:p.Arg527His
NP_733822.1:p.Arg527His
LRG_254t1:c.1580G>A
LRG_254t2:c.1580G>A
LRG_254:g.59632G>A
LRG_254p1:p.Arg527His
NC_000001.10:g.156106995G>A
NM_001257374.1:c.1244G>A
NM_005572.3:c.1580G>A
NM_170707.2:c.1580G>A
NM_170707.3:c.1580G>A
P02545:p.Arg527His

Protein change:

R415H; ARG527HIS

Links:

UniProtKB: P02545#VAR_018727; OMIM: 150330.0021; dbSNP: rs57520892

NCBI 1000 Genomes Browser:

rs57520892

Molecular consequence:

NM_001257374.3:c.1244G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.1337G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1580G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1580G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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
SCV000088439	Epithelial Biology; Institute of Medical Biology, Singapore	no classification provided	not provided	not provided	not provided
SCV000233098	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Jun 19, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000234705	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 16, 2021)	germline	clinical testing	Citation Link,
SCV002017155	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 28, 2020)	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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C.

Novelli G, Muchir A, Sangiuolo F, Helbling-Leclerc A, D'Apice MR, Massart C, Capon F, Sbraccia P, Federici M, Lauro R, Tudisco C, Pallotta R, Scarano G, Dallapiccola B, Merlini L, Bonne G.

Am J Hum Genet. 2002 Aug;71(2):426-31. Epub 2002 Jun 19.

PubMed [citation]

PMID:: 12075506
PMCID:: PMC379176

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 Epithelial Biology; Institute of Medical Biology, Singapore, SCV000088439.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000233098.5

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

#	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		1	not provided	not provided	not provided

From GeneDx, SCV000234705.16

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

Description

Published functional studies demonstrate a damaging effect: failure to restore p16ink4A/pRB pathway signaling, increased sensitivity to ionizing radiation, and destabilization of heterochromatin-associated proteins (Filesi et al., 2005; Nitta et al., 2006; di Masi et al., 2008); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23891399, 24375749, 25637381, 18604166, 12075506, 14627682, 12788894, 16046620, 19764019, 28663758, 25823658, 19084400, 17848409, 31589614, 32041611, 32376792, 34135346, 33422685, 10939567, 33038109, 15473259, 29854317, 25324471, 16809772, 10080180, 31383942)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002017155.3

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

#	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: Dec 22, 2024

ClinVar

Relating variation to medicine