NM_000218.3(KCNQ1):c.532G>A (p.Ala178Thr) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 1, 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:: RCV000182081.16

Allele description [Variation Report for NM_000218.3(KCNQ1):c.532G>A (p.Ala178Thr)]

NM_000218.3(KCNQ1):c.532G>A (p.Ala178Thr)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000218.3(KCNQ1):c.532G>A (p.Ala178Thr)

Other names:

p.A178T:GCC>ACC

HGVS:

NC_000011.10:g.2570682G>A
NG_008935.1:g.130692G>A
NM_000218.3:c.532G>AMANE SELECT
NM_001406836.1:c.532G>A
NM_001406837.1:c.262G>A
NM_181798.2:c.151G>A
NP_000209.2:p.Ala178Thr
NP_000209.2:p.Ala178Thr
NP_001393765.1:p.Ala178Thr
NP_001393766.1:p.Ala88Thr
NP_861463.1:p.Ala51Thr
NP_861463.1:p.Ala51Thr
LRG_287t1:c.532G>A
LRG_287t2:c.151G>A
LRG_287:g.130692G>A
LRG_287p1:p.Ala178Thr
LRG_287p2:p.Ala51Thr
NC_000011.9:g.2591912G>A
NM_000218.2:c.532G>A
NM_181798.1:c.151G>A
NR_040711.2:n.425G>A
P51787:p.Ala178Thr

Protein change:

A178T

Links:

UniProtKB: P51787#VAR_009920; dbSNP: rs120074177

NCBI 1000 Genomes Browser:

rs120074177

Molecular consequence:

NM_000218.3:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406836.1:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406837.1:c.262G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181798.2:c.151G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000234384	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 23, 2022)	germline	clinical testing	Citation Link,
SCV002051661	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004010037	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Apr 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000234384

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 23, 2022)

germline

clinical testing

Citation Link,

SCV002051661

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 30, 2021)

germline

clinical testing

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

SCV004010037

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Apr 1, 2023)

germline

clinical testing

Citation Link

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
not provided	germline	yes	2	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 GeneDx, SCV000234384.15

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

Description

Identified in several patients with LQTS referred for genetic testing at GeneDx and in published literature (Tanaka et al., 1997; Splawski et al., 2000; Jons et al., 2009; Kapplinger et al., 2009; Kwok et al., 2018); Not observed at a significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate that this variant severely disrupts channel trafficking (Harmer et al., 2014; Mousavi et al., 2015); 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: 10973849, 25705178, 30530868, 22378279, 25637381, 22456477, 9024139, 12388934, 19490272, 26546361, 28991257, 19716085, 32368696, 34426522, 24912595)

#	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 Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV002051661.3

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

Description

PS3, PM2, PM1, PP3

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV004010037.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

Description

KCNQ1: PS2, PM5, PS4:Moderate, PM2:Supporting, PP1

#	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		2	not provided	not provided	not provided

Last Updated: May 1, 2024

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