NM_020822.3(KCNT1):c.2800G>A (p.Ala934Thr) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 1, 2022
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:: RCV000494477.25

Allele description [Variation Report for NM_020822.3(KCNT1):c.2800G>A (p.Ala934Thr)]

NM_020822.3(KCNT1):c.2800G>A (p.Ala934Thr)

Gene:

KCNT1:potassium sodium-activated channel subfamily T member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.3

Genomic location:

Preferred name:

NM_020822.3(KCNT1):c.2800G>A (p.Ala934Thr)

HGVS:

NC_000009.12:g.135779429G>A
NG_033070.1:g.82245G>A
NM_001272003.2:c.2665G>A
NM_020822.3:c.2800G>AMANE SELECT
NP_001258932.1:p.Ala889Thr
NP_065873.2:p.Ala934Thr
NC_000009.11:g.138671275G>A
NM_020822.2:c.2800G>A

Protein change:

A889T; ALA934THR

Links:

OMIM: 608167.0002; dbSNP: rs397515403

NCBI 1000 Genomes Browser:

rs397515403

Molecular consequence:

NM_001272003.2:c.2665G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020822.3:c.2800G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

probably has functional consequence

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
SCV000582546	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 7, 2022)	germline	clinical testing	Citation Link,
SCV001247128	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Nov 1, 2022)	germline	clinical testing	Citation Link,
SCV002023233	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 26, 2019)	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

SCV000582546

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 7, 2022)

germline

clinical testing

Citation Link,

SCV001247128

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

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

Pathogenic
(Nov 1, 2022)

germline

clinical testing

Citation Link,

SCV002023233

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 26, 2019)

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
not provided	germline	yes	4	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, SCV000582546.6

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

Description

Published functional studies demonstrate a damaging effect as the p.A934T variant causes a marked increase in KCNT1 protein function; the mutant channel activates significantly more quickly than wild-type channels with greater current amplitude (Barcia et al., 2012; Milligan et al., 2014; Kim et al., 2014); Not observed in large population cohorts (gnomAD); 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: 23599387, 26122718, 23086397, 25482562, 27620904, 26785903, 26441003, 26140313, 26740507, 27779742, 27064559, 29390993, 30182498, 31054490, 31487502, 30847371, 30782581, 31872048, 31532509, 32139178, 24591078, 29100083, 32167590)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001247128.20

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

Description

KCNT1: PS2, PM1, PM2, PS4:Moderate, PS3:Supporting

#	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		4	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002023233.3

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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