NM_000501.4(ELN):c.1621C>T (p.Arg541Ter) AND Supravalvar aortic stenosis

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 15, 2023
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:: RCV000018207.29

Allele description

NM_000501.4(ELN):c.1621C>T (p.Arg541Ter)

Genes:

ELN-AS1:ELN antisense RNA 1 [Gene - HGNC]
ELN:elastin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q11.23

Genomic location:

Preferred name:

NM_000501.4(ELN):c.1621C>T (p.Arg541Ter)

Other names:

p.R541*:CGA>TGA

HGVS:

NC_000007.14:g.74060184C>T
NG_009261.1:g.37088C>T
NM_000501.4:c.1621C>TMANE SELECT
NM_001081752.3:c.1534C>T
NM_001081753.3:c.1579C>T
NM_001081754.3:c.1636C>T
NM_001081755.3:c.1564C>T
NM_001278912.2:c.1621C>T
NM_001278913.2:c.1378C>T
NM_001278914.2:c.1549C>T
NM_001278915.2:c.1639C>T
NM_001278916.2:c.1477+137C>T
NM_001278917.2:c.1591C>T
NM_001278918.2:c.1354C>T
NM_001278939.2:c.1708C>T
NP_000492.2:p.Arg541Ter
NP_001075221.1:p.Arg512Ter
NP_001075222.1:p.Arg527Ter
NP_001075223.1:p.Arg546Ter
NP_001075224.1:p.Arg522Ter
NP_001265841.1:p.Arg541Ter
NP_001265842.1:p.Arg460Ter
NP_001265843.1:p.Arg517Ter
NP_001265844.1:p.Arg547Ter
NP_001265846.1:p.Arg531Ter
NP_001265847.1:p.Arg452Ter
NP_001265868.1:p.Arg570Ter
NC_000007.13:g.73474514C>T
NM_000501.2:c.1621C>T
NM_000501.3:c.1621C>T
NM_001278917.1:c.1591C>T

Nucleotide change:

1621C-T

Protein change:

R452*; ARG570TER

Links:

OMIM: 130160.0004; OMIM: 130160.0019; dbSNP: rs137854453

NCBI 1000 Genomes Browser:

rs137854453

Molecular consequence:

NM_001278916.2:c.1477+137C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000501.4:c.1621C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001081752.3:c.1534C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001081753.3:c.1579C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001081754.3:c.1636C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001081755.3:c.1564C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001278912.2:c.1621C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001278913.2:c.1378C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001278914.2:c.1549C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001278915.2:c.1639C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001278917.2:c.1591C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001278918.2:c.1354C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001278939.2:c.1708C>T - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

effect on RNA splicing [PubMedVariation Ontology: 0362]

Observations:

Condition(s)

Name:: Supravalvar aortic stenosis (SVAS)
Synonyms:: Supravalvar aortic stenosis, Eisenberg type
Identifiers:: MONDO: MONDO:0008504; MedGen: C0003499; Orphanet: 3193; OMIM: 185500; Human Phenotype Ontology: HP:0004381

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PREDICTED: hepatocyte nuclear factor 1-beta [Lepisosteus oculatus]
gi|573906510|ref|XP_006640975.1|

Protein
5 eggcsite.comfoC (1)
BioProject
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Treponema pallidum subsp. pallidum str. Nichols
Causative agent of syphilis

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000038486	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 2000)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 9215670, 11175284
SCV001739478	Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 28, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004102628	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 15, 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

SCV000038486

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 2000)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV001739478

Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 28, 2020)

germline

clinical testing

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

SCV004102628

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 15, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
East asia	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis.

Li DY, Toland AE, Boak BB, Atkinson DL, Ensing GJ, Morris CA, Keating MT.

Hum Mol Genet. 1997 Jul;6(7):1021-8.

PubMed [citation]

PMID:: 9215670

Elastin: mutational spectrum in supravalvular aortic stenosis.

Metcalfe K, Rucka AK, Smoot L, Hofstadler G, Tuzler G, McKeown P, Siu V, Rauch A, Dean J, Dennis N, Ellis I, Reardon W, Cytrynbaum C, Osborne L, Yates JR, Read AP, Donnai D, Tassabehji M.

Eur J Hum Genet. 2000 Dec;8(12):955-63.

PubMed [citation]

PMID:: 11175284

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000038486.1

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

Description

In a sporadic case of SVAS (185500), Li et al. (1997) found a nonsense mutation: a C-to-T transition at nucleotide 1708, resulting in conversion of arginine-570 to a premature stop codon in exon 25 (R570X). DNA samples could not be obtained from the parents of the proband.

Metcalfe et al. (2000) detected the R570X mutation in a sporadic case of SVAS with peripheral pulmonary artery stenosis and bilateral inguinal hernias.

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

From Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital, SCV001739478.1

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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV004102628.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 17, 2024

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