NM_000218.3(KCNQ1):c.957_958delinsTT (p.Pro320Ser) AND Long QT syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 2, 2022
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:: RCV003040375.2

Allele description [Variation Report for NM_000218.3(KCNQ1):c.957_958delinsTT (p.Pro320Ser)]

NM_000218.3(KCNQ1):c.957_958delinsTT (p.Pro320Ser)

Gene:

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

Variant type:

Indel

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.957_958delinsTT (p.Pro320Ser)

HGVS:

NC_000011.10:g.2583470_2583471delinsTT
NG_008935.1:g.143480_143481delinsTT
NM_000218.3:c.957_958delinsTTMANE SELECT
NM_001406836.1:c.957_958delGCinsTT
NM_001406837.1:c.687_688delGCinsTT
NM_001406838.1:c.513_514delGCinsTT
NM_181798.2:c.576_577delGCinsTT
NP_000209.2:p.Pro320Ser
NP_000209.2:p.Pro320Ser
NP_001393765.1:p.Pro320Ser
NP_001393766.1:p.Pro230Ser
NP_001393767.1:p.Pro172Ser
NP_861463.1:p.Pro193Ser
NP_861463.1:p.Pro193Ser
LRG_287t1:c.957_958delGCinsTT
LRG_287t2:c.576_577delinsTT
LRG_287:g.143480_143481delinsTT
LRG_287p1:p.Pro320Ser
LRG_287p2:p.Pro193Ser
NC_000011.9:g.2604700_2604701delinsTT
NM_000218.2:c.957_958delGCinsTT
NM_181798.1:c.576_577delinsTT
NR_040711.2:n.850_851delGCinsTT

Protein change:

P172S

Molecular consequence:

NM_000218.3:c.957_958delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.957_958delGCinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.687_688delGCinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001406838.1:c.513_514delGCinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.576_577delGCinsTT - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003353597	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 2, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19540844, 22949429, 23392653, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003353597

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 2, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Biophysical characterization of KCNQ1 P320 mutations linked to long QT syndrome 1.

Thomas D, Khalil M, Alter M, Schweizer PA, Karle CA, Wimmer AB, Licka M, Katus HA, Koenen M, Ulmer HE, Zehelein J.

J Mol Cell Cardiol. 2010 Jan;48(1):230-7. doi: 10.1016/j.yjmcc.2009.06.009. Epub 2009 Jun 21.

PubMed [citation]

PMID:: 19540844

Phylogenetic and physicochemical analyses enhance the classification of rare nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome.

Giudicessi JR, Kapplinger JD, Tester DJ, Alders M, Salisbury BA, Wilde AA, Ackerman MJ.

Circ Cardiovasc Genet. 2012 Oct 1;5(5):519-28. doi: 10.1161/CIRCGENETICS.112.963785. Epub 2012 Sep 4.

PubMed [citation]

PMID:: 22949429
PMCID:: PMC3705705

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV003353597.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro320His amino acid residue in KCNQ1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19540844, 22949429). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This missense change has been observed in individuals with clinical features of long QT syndrome (PMID: 23392653; Invitae). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 320 of the KCNQ1 protein (p.Pro320Ser).

#	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: Feb 20, 2024

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