NM_020822.3(KCNT1):c.2849G>A (p.Arg950Gln) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 29, 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:: RCV000498228.13

Allele description [Variation Report for NM_020822.3(KCNT1):c.2849G>A (p.Arg950Gln)]

NM_020822.3(KCNT1):c.2849G>A (p.Arg950Gln)

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.2849G>A (p.Arg950Gln)

HGVS:

NC_000009.12:g.135784031G>A
NG_033070.1:g.86847G>A
NM_001272003.2:c.2714G>A
NM_020822.3:c.2849G>AMANE SELECT
NP_001258932.1:p.Arg905Gln
NP_065873.2:p.Arg950Gln
NC_000009.11:g.138675877G>A
NM_020822.2:c.2849G>A

Protein change:

R905Q

Links:

Molecular consequence:

NM_001272003.2:c.2714G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020822.3:c.2849G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Mus musculus olfactory receptor family 5 subfamily H member 17 (Or5h17), mRNA
Mus musculus olfactory receptor family 5 subfamily H member 17 (Or5h17), mRNA
gi|112983467|ref|NM_146485.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000589673	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 29, 2022)	germline	clinical testing	Citation Link,
SCV001447907	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	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

SCV000589673

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 29, 2022)

germline

clinical testing

Citation Link,

SCV001447907

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 23, 2020)

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	yes	not provided	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	1	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 Eurofins Ntd Llc (ga), SCV000340255.4

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

#	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		1	not provided	not provided	not provided

From GeneDx, SCV000589673.5

#	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 gain-of-function phenotype (Dilena et al., 2018); Not observed at significant frequency 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: 29694806, 29056246, 26122718, 27029629, 29196578, 28488083, 29100083, 31487502, 30847371, 32167590, 30112700)

#	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 Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001447907.1

#	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	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000340255	Eurofins Ntd Llc (ga)	flagged submission Reason: Older and outlier claim with insufficient supporting evidence Notes: None (EGL Classification Definitions 2015)	Uncertain significance (Mar 28, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000340255

Eurofins Ntd Llc (ga)

flagged submission

Reason: Older and outlier claim with insufficient supporting evidence

Notes: None

(EGL Classification Definitions 2015)

Uncertain significance
(Mar 28, 2016)

germline

clinical testing

Citation Link

Last Updated: Sep 29, 2024

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