NM_020822.3(KCNT1):c.1038C>A (p.Phe346Leu) AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Jul 2, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001219954.2

Allele description [Variation Report for NM_020822.3(KCNT1):c.1038C>A (p.Phe346Leu)]

NM_020822.3(KCNT1):c.1038C>A (p.Phe346Leu)

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.1038C>A (p.Phe346Leu)
HGVS:
  • NC_000009.12:g.135765033C>A
  • NG_033070.1:g.67849C>A
  • NM_001272003.2:c.903C>A
  • NM_020822.3:c.1038C>AMANE SELECT
  • NP_001258932.1:p.Phe301Leu
  • NP_065873.2:p.Phe346Leu
  • NC_000009.11:g.138656879C>A
  • NM_020822.2:c.1038C>A
Protein change:
F301L
Molecular consequence:
  • NM_001272003.2:c.903C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020822.3:c.1038C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Early infantile epileptic encephalopathy 14 (DEE14)
Synonyms:
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14
Identifiers:
MONDO: MONDO:0013989; MedGen: C3554195; Orphanet: 293181; OMIM: 614959
Name:
Epilepsy, nocturnal frontal lobe, 5 (ENFL5)
Synonyms:
CILIARY DYSKINESIA, PRIMARY, 28, WITHOUT SITUS INVERSUS; CILIARY DYSKINESIA, PRIMARY, 28, WITH SITUS INVERSUS
Identifiers:
MONDO: MONDO:0014002; MedGen: C3554306; Orphanet: 98784; OMIM: 615005

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001391921Invitaecriteria provided, single submitter
Likely pathogenic
(Jul 2, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing.

Rim JH, Kim SH, Hwang IS, Kwon SS, Kim J, Kim HW, Cho MJ, Ko A, Youn SE, Kim J, Lee YM, Chung HJ, Lee JS, Kim HD, Choi JR, Lee ST, Kang HC.

BMC Med Genomics. 2018 Feb 1;11(1):6. doi: 10.1186/s12920-018-0320-7.

PubMed [citation]
PMID:
29390993
PMCID:
PMC5796507

Exome sequencing identifies molecular diagnosis in children with drug-resistant epilepsy.

Tsang MH, Leung GK, Ho AC, Yeung KS, Mak CC, Pei SL, Yu MH, Kan AS, Chan KY, Kwong KL, Lee SL, Yung AW, Fung CW, Chung BH.

Epilepsia Open. 2019 Mar;4(1):63-72. doi: 10.1002/epi4.12282.

PubMed [citation]
PMID:
30868116
PMCID:
PMC6398105
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001391921.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces phenylalanine with leucine at codon 346 of the KCNT1 protein (p.Phe346Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with early infantile epileptic encephalopathy (PMID: 29390993, 30868116, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 10, 2021

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