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

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(2);Uncertain significance(1) (Last evaluated: Oct 23, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000498228.4

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:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000340255EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Mar 28, 2016)
germlineclinical testing

Citation Link,

SCV000589673GeneDxcriteria provided, single submitter
Pathogenic
(Jun 21, 2018)
germlineclinical testing

Citation Link,

SCV001447907Institute of Medical Genetics and Applied Genomics, University Hospital Tübingencriteria provided, single submitter
Pathogenic
(Oct 23, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot provided1not providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical 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 EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000340255.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV000589673.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The R950Q variant in the KCNT1 gene has been previously reported as a de novo change in multiple individuals previously tested at GeneDx and in the published literature with epilepsy (Moller et al., 2015; Hildebrand et al., 2016). The R950Q variant is not observed in large population cohorts (Lek et al., 2016). The R950Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect.

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

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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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