NM_020822.3(KCNT1):c.1885A>G (p.Lys629Glu) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Aug 31, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001383750.1

Allele description [Variation Report for NM_020822.3(KCNT1):c.1885A>G (p.Lys629Glu)]

NM_020822.3(KCNT1):c.1885A>G (p.Lys629Glu)

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.1885A>G (p.Lys629Glu)
HGVS:
  • NC_000009.12:g.135770972A>G
  • NG_033070.1:g.73788A>G
  • NM_001272003.2:c.1750A>G
  • NM_020822.3:c.1885A>GMANE SELECT
  • NP_001258932.1:p.Lys584Glu
  • NP_065873.2:p.Lys629Glu
  • NC_000009.11:g.138662818A>G
  • NM_020822.2:c.1885A>G
Protein change:
K584E
Links:
dbSNP: rs1057522978
NCBI 1000 Genomes Browser:
rs1057522978
Molecular consequence:
  • NM_001272003.2:c.1750A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020822.3:c.1885A>G - 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
SCV001583005Invitaecriteria provided, single submitter
Pathogenic
(Aug 31, 2020)
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

Gene mutation analysis of 175 Chinese patients with early-onset epileptic encephalopathy.

Zhang Q, Li J, Zhao Y, Bao X, Wei L, Wang J.

Clin Genet. 2017 May;91(5):717-724. doi: 10.1111/cge.12901. Epub 2017 Feb 16.

PubMed [citation]
PMID:
27779742

Quinidine in the treatment of KCNT1-positive epilepsies.

Mikati MA, Jiang YH, Carboni M, Shashi V, Petrovski S, Spillmann R, Milligan CJ, Li M, Grefe A, McConkie A, Berkovic S, Scheffer I, Mullen S, Bonner M, Petrou S, Goldstein D.

Ann Neurol. 2015 Dec;78(6):995-9. doi: 10.1002/ana.24520. Epub 2015 Nov 18.

PubMed [citation]
PMID:
26369628
PMCID:
PMC4811613
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001583005.1

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

Description

This sequence change replaces lysine with glutamic acid at codon 629 of the KCNT1 protein (p.Lys629Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with KCNT1-related conditions (PMID: 27779742, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 388032). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). This variant disrupts the p.Lys629 amino acid residue in KCNT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26369628). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 14, 2021

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