NM_000218.3(KCNQ1):c.1534del (p.Ala512fs) AND Jervell and Lange-Nielsen syndrome 1

Germline classification:: Pathogenic (1 submission)
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:: RCV000590985.3

Allele description [Variation Report for NM_000218.3(KCNQ1):c.1534del (p.Ala512fs)]

NM_000218.3(KCNQ1):c.1534del (p.Ala512fs)

Gene:

KCNQ1:potassium voltage-gated channel subfamily Q member 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.1534del (p.Ala512fs)

HGVS:

NC_000011.10:g.2768863del
NG_008935.1:g.328873del
NM_000218.3:c.1534delMANE SELECT
NM_001406836.1:c.1438delG
NM_001406837.1:c.1264delG
NM_001406838.1:c.994delG
NM_181798.2:c.1153delG
NP_000209.2:p.Ala512Profs
NP_000209.2:p.Ala512fs
NP_001393765.1:p.Ala480Profs
NP_001393766.1:p.Ala422Profs
NP_001393767.1:p.Ala332Profs
NP_861463.1:p.Ala385Profs
NP_861463.1:p.Ala385fs
LRG_287t1:c.1534del
LRG_287t2:c.1153del
LRG_287:g.328873del
LRG_287p1:p.Ala512Profs
LRG_287p2:p.Ala385fs
NC_000011.9:g.2790093del
NM_000218.2:c.1534delG
NM_000218.2:c.1534delG
NM_181798.1:c.1153del
NR_040711.2:n.1427delG

Protein change:

A385fs

Links:

dbSNP: rs1554919471

NCBI 1000 Genomes Browser:

rs1554919471

Molecular consequence:

NM_000218.3:c.1534del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.1438delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.1264delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406838.1:c.994delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.1153delG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Jervell and Lange-Nielsen syndrome 1 (JLNS1)
Synonyms:: Deafness, congenital, and functional heart disease; Prolonged QT interval in EKG and sudden death; Cardioauditory syndrome of Jervell and Lange-Nielsen; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0024540; MedGen: C4551509; Orphanet: 768; Orphanet: 90647; OMIM: 220400

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
SCV000584010	Biotechnology Research Center, Pasteur Institute of Iran	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 29372044

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000584010

Biotechnology Research Center, Pasteur Institute of Iran

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

research

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Iranian	germline	yes	3	1	not provided	not provided	not provided	research
Iranian	germline	no	3	1	not provided	not provided	not provided	research

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

Novel frameshift mutation in the KCNQ1 gene responsible for Jervell and Lange-Nielsen syndrome.

Amirian A, Dalili SM, Zafari Z, Saber S, Karimipoor M, Akbari V, Fazelifar AF, Zeinali S.

Iran J Basic Med Sci. 2018 Jan;21(1):108-111. doi: 10.22038/IJBMS.2017.23207.5908.

PubMed [citation]

PMID:: 29372044
PMCID:: PMC5776430

Details of each submission

From Biotechnology Research Center, Pasteur Institute of Iran, SCV000584010.1

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

Description

According to the ACMG standards and guidelines these findings are evidence of pathogenicity. 1: The mutation in the family was a LOF in the KCNQ1 gene where LOF is a known mechanism of JLNS (PVS1). 2: The mutation has never been reported in ExAC or 1000G (PM2) 3: this KCNQ1 gene mutation results in the truncated protein (PM4)

#	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		3	not provided	1	not provided
2	germline	no	not provided	not provided	not provided		3	not provided	1	not provided

Last Updated: Mar 26, 2023

ClinVar

Relating variation to medicine