NM_000218.3(KCNQ1):c.919del (p.Val307fs) AND Congenital long QT syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 27, 2016
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:: RCV004017886.2

Allele description [Variation Report for NM_000218.3(KCNQ1):c.919del (p.Val307fs)]

NM_000218.3(KCNQ1):c.919del (p.Val307fs)

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.919del (p.Val307fs)

HGVS:

NC_000011.10:g.2572984del
NG_008935.1:g.132994del
NM_000218.3:c.919delMANE SELECT
NM_001406836.1:c.919delG
NM_001406837.1:c.649delG
NM_181798.2:c.538delG
NP_000209.2:p.Val307Trpfs
NP_000209.2:p.Val307fs
NP_001393765.1:p.Val307Trpfs
NP_001393766.1:p.Val217Trpfs
NP_861463.1:p.Val180Trpfs
NP_861463.1:p.Val180fs
LRG_287t1:c.919del
LRG_287t2:c.538del
LRG_287:g.132994del
LRG_287p1:p.Val307Trpfs
LRG_287p2:p.Val180fs
NC_000011.10:g.2572984delG
NC_000011.9:g.2594209del
NC_000011.9:g.2594214del
NM_000218.2:c.919delG
NM_181798.1:c.538del
NR_040711.2:n.812delG

Protein change:

V180fs

Links:

dbSNP: rs2133733071

NCBI 1000 Genomes Browser:

rs2133733071

Molecular consequence:

NM_000218.3:c.919del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406836.1:c.919delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406837.1:c.649delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181798.2:c.538delG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Congenital long QT syndrome (RWS)
Synonyms:: Familial long QT syndrome; Romano-Ward syndrome; Ventricular fibrillation with prolonged QT interval
Identifiers:: MONDO: MONDO:0019171; MedGen: C1141890; Orphanet: 768; OMIM: PS192500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004848019	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Dec 27, 2016)	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

SCV004848019

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Dec 27, 2016)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848019.1

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

Description

The p.Val307fs variant in KCNQ1 has not been previously reported in individuals with long QT syndrome and was absent from large population studies, though the ability of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 307 and leads to a premature termination codon 47 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the KCNQ1 gene is an established disease mechanism in Long QT syndrome. In summary, although additional studies are required to fully establish its clinical significance, the p.Val307fs variant is likely pathogenic.

#	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

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