The variant c.916C>T, p.(Arg306Cys) was identified in an individual with neurodevelopmental disorder (NDD) and classified as Pathogenic according to ACMG guidelines. Inheritance for this variant was not maternal.The variant likely explains the NDD in this individual.
ClinVar Genomic variation as it relates to human health
NM_004975.4(KCNB1):c.916C>T (p.Arg306Cys)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(12)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
12
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_004975.4(KCNB1):c.916C>T (p.Arg306Cys)
Variation ID: 449693 Accession: VCV000449693.28
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 20q13.13 20: 49374644 (GRCh38) [ NCBI UCSC ] 20: 47991181 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 19, 2017 Jul 23, 2024 Jul 7, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_004975.4:c.916C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004966.1:p.Arg306Cys missense NC_000020.11:g.49374644G>A NC_000020.10:g.47991181G>A NG_041781.2:g.113001C>T - Protein change
- R306C
- Other names
- -
- Canonical SPDI
- NC_000020.11:49374643:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
Severe decrease in peak current; Functional Epilepsy Nomenclature for Ion Channels [ FENICS-0087]
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| KCNB1 | - | - |
GRCh38 GRCh37 |
735 | 750 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, single submitter
|
Jul 27, 2022 | RCV000520238.6 | |
| Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Jul 7, 2023 | RCV000688503.25 | |
| Likely pathogenic (1) |
no assertion criteria provided
|
- | RCV001003632.3 | |
|
developmental encephalopathy with epilepsy
|
Pathogenic (1) |
no assertion criteria provided
|
Dec 1, 2019 | RCV001249560.4 |
| Pathogenic (1) |
criteria provided, single submitter
|
Aug 3, 2020 | RCV001255349.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Mar 1, 2019 | RCV000782146.4 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Mar 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Epileptic encephalopathy
Affected status: yes
Allele origin:
de novo
|
Laboratoire de Génétique Moléculaire Institut de Recherche Necker Enfants Malades, CHU Paris - Hôpital Necker-Enfants Malades
Accession: SCV000920610.1
First in ClinVar: Jun 09, 2019 Last updated: Jun 09, 2019 |
|
|
|
Pathogenic
(Aug 03, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Intellectual disability
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001431679.1
First in ClinVar: Sep 14, 2020 Last updated: Sep 14, 2020 |
Comment:
The variant c.916C>T, p.(Arg306Cys) was identified in an individual with neurodevelopmental disorder (NDD) and classified as Pathogenic according to ACMG guidelines. Inheritance for this variant … (more)
The variant c.916C>T, p.(Arg306Cys) was identified in an individual with neurodevelopmental disorder (NDD) and classified as Pathogenic according to ACMG guidelines. Inheritance for this variant was not maternal.The variant likely explains the NDD in this individual. (less)
|
|
|
Pathogenic
(Mar 15, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Developmental and epileptic encephalopathy, 26
Affected status: yes
Allele origin:
de novo
|
New York Genome Center
Study: CSER-NYCKidSeq
Accession: SCV002098958.1 First in ClinVar: Feb 26, 2022 Last updated: Feb 26, 2022 |
Comment:
The de novo c.916C>T (p.Arg306Cys variant in exon 2 of 2 of KCNB1 has been reported in multiple affected individuals in the available literature [PMID: … (more)
The de novo c.916C>T (p.Arg306Cys variant in exon 2 of 2 of KCNB1 has been reported in multiple affected individuals in the available literature [PMID: 26477325.; PMID: 27652284; PMID: 29264397; PMID: 31513310; PMID: 32469098]. It is also submitted multiple times in ClinVar database by independent clinical laboratories and classified as Pathogenic/Likely Pathogenic (VarID: 449693). This variant is absent in gnomAD suggesting it is not a common benign variant in the populations represented in this database. In silico predictors suggest this variant is Pathogenic (REVEL; score: 0.86) and damaging (SIFT; score: 0). Functional studies have shown this variant in the voltage sensor domain S4, disrupts sensitivity and cooperativity of the sensor and results in loss of voltage sensing [2]. Given this evidence the de novo c.916C>T (p.Arg306Cys) variant identified in the KCNB1 gene is classified as Pathogenic. (less)
Clinical Features:
Seizure (present) , Intellectual disability (present)
Secondary finding: no
|
|
|
Pathogenic
(Apr 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Developmental and epileptic encephalopathy, 26
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001429443.2
First in ClinVar: Aug 16, 2020 Last updated: Apr 30, 2022 |
Comment:
_x000D_ Criteria applied: PS2, PS4, PM1_SUP, PM2_SUP, PP2, PP3
|
|
|
Pathogenic
(Jun 30, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Developmental and epileptic encephalopathy, 26
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo,
germline
|
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001430001.2
First in ClinVar: Aug 21, 2020 Last updated: Dec 24, 2022 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Cognitive impairment (present) , Autism (present) , Intellectual disability (present)
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Hypopigmentation of the skin (present) , EEG abnormality (present) , Intellectual disability (present) , Cafe-au-lait spot (present) , Movement disorder (present) , Delayed speech and … (more)
Hypopigmentation of the skin (present) , EEG abnormality (present) , Intellectual disability (present) , Cafe-au-lait spot (present) , Movement disorder (present) , Delayed speech and language development (present) (less)
|
|
|
Pathogenic
(Jul 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000618040.4
First in ClinVar: Dec 19, 2017 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate a damaging effect due to exhibiting higher resting membrane potentials, higher thresholds for action potential firing, and dramatically reduced ability of … (more)
Published functional studies demonstrate a damaging effect due to exhibiting higher resting membrane potentials, higher thresholds for action potential firing, and dramatically reduced ability of repetitive firing (Saitsu et al., 2015); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29264397, 31600826, 32581362, 32954514, 32725632, 26477325, 31513310, 32469098) (less)
|
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: not provided
|
Developmental and epileptic encephalopathy, 26
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, University Hospital of Duesseldorf
Accession: SCV004171181.1
First in ClinVar: Dec 02, 2023 Last updated: Dec 02, 2023 |
|
|
|
Pathogenic
(Jul 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Developmental and epileptic encephalopathy, 26
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000816118.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects KCNB1 function (PMID: 26477325). Advanced modeling … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects KCNB1 function (PMID: 26477325). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNB1 protein function. ClinVar contains an entry for this variant (Variation ID: 449693). This missense change has been observed in individual(s) with early infantile epileptic encephalopathy (PMID: 26477325, 28806457, 29264397). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 306 of the KCNB1 protein (p.Arg306Cys). (less)
|
|
|
Pathogenic
(Feb 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Developmental and epileptic encephalopathy, 26
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002557045.2
First in ClinVar: Aug 04, 2022 Last updated: Jul 23, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative, loss of function and gain … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative, loss of function and gain of function are known mechanisms of disease in this gene and are associated with developmental and epileptic encephalopathy 26 (MIM#616056). However, the ultimate result of each mechanism is channel dysfunction (PMID: 31512327). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0602 - Variant is located in a cluster of pathogenic variants, S4 of the voltage-sensing domain (PMID: 26477325). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. The alternative change to a histidine has been reported once as likely pathogenic in ClinVar. (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This is a recurrent de novo variant in individuals with developmental and epileptic encephalopathy (ClinVar, PMID: 26477325, 29264397, 28806457, 31513310). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Functional studies using transfected Neuro2a cells showed that the variant disrupts sensitivity and cooperativity of the sensor (PMID: 26477325). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: research
|
Myoclonic absence seizure
Affected status: yes
Allele origin:
unknown
|
NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV001162059.1
First in ClinVar: Feb 27, 2020 Last updated: Feb 27, 2020 |
Number of individuals with the variant: 1
Sex: female
|
|
|
Pathogenic
(Dec 01, 2019)
|
no assertion criteria provided
Method: clinical testing
|
developmental encephalopathy with epilepsy
Affected status: yes
Allele origin:
de novo
|
Laboratoire de Génétique Moléculaire Institut de Recherche Necker Enfants Malades, CHU Paris - Hôpital Necker-Enfants Malades
Accession: SCV001423128.1
First in ClinVar: Jul 19, 2020 Last updated: Jul 19, 2020 |
|
|
|
not provided
(-)
|
no classification provided
Method: in vitro
|
not provided
Affected status: not applicable
Allele origin:
not applicable
|
Kearney Laboratory, Northwestern University Feinberg School of Medicine
Accession: SCV004024586.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
Method: Automated patch clamp recording
Result:
Severe decrease in peak current (FENICS-0087)
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
The de novo c.916C>T (p.Arg306Cys variant in exon 2 of 2 of KCNB1 has been reported in multiple affected individuals in the available literature [PMID: 26477325.; PMID: 27652284; PMID: 29264397; PMID: 31513310; PMID: 32469098]. It is also submitted multiple times in ClinVar database by independent clinical laboratories and classified as Pathogenic/Likely Pathogenic (VarID: 449693). This variant is absent in gnomAD suggesting it is not a common benign variant in the populations represented in this database. In silico predictors suggest this variant is Pathogenic (REVEL; score: 0.86) and damaging (SIFT; score: 0). Functional studies have shown this variant in the voltage sensor domain S4, disrupts sensitivity and cooperativity of the sensor and results in loss of voltage sensing [2]. Given this evidence the de novo c.916C>T (p.Arg306Cys) variant identified in the KCNB1 gene is classified as Pathogenic.
Comment:
_x000D_ Criteria applied: PS2, PS4, PM1_SUP, PM2_SUP, PP2, PP3
Comment:
Published functional studies demonstrate a damaging effect due to exhibiting higher resting membrane potentials, higher thresholds for action potential firing, and dramatically reduced ability of repetitive firing (Saitsu et al., 2015); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29264397, 31600826, 32581362, 32954514, 32725632, 26477325, 31513310, 32469098)
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects KCNB1 function (PMID: 26477325). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNB1 protein function. ClinVar contains an entry for this variant (Variation ID: 449693). This missense change has been observed in individual(s) with early infantile epileptic encephalopathy (PMID: 26477325, 28806457, 29264397). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 306 of the KCNB1 protein (p.Arg306Cys).
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative, loss of function and gain of function are known mechanisms of disease in this gene and are associated with developmental and epileptic encephalopathy 26 (MIM#616056). However, the ultimate result of each mechanism is channel dysfunction (PMID: 31512327). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0602 - Variant is located in a cluster of pathogenic variants, S4 of the voltage-sensing domain (PMID: 26477325). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. The alternative change to a histidine has been reported once as likely pathogenic in ClinVar. (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This is a recurrent de novo variant in individuals with developmental and epileptic encephalopathy (ClinVar, PMID: 26477325, 29264397, 28806457, 31513310). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Functional studies using transfected Neuro2a cells showed that the variant disrupts sensitivity and cooperativity of the sensor (PMID: 26477325). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|---|---|---|---|
|
Severe decrease in peak current
|
Method citation(s):
|
|
Kearney Laboratory, Northwestern University Feinberg School of Medicine
Accession: SCV004024586.1
|
|
Comment:
The variant c.916C>T, p.(Arg306Cys) was identified in an individual with neurodevelopmental disorder (NDD) and classified as Pathogenic according to ACMG guidelines. Inheritance for this variant was not maternal.The variant likely explains the NDD in this individual.
Comment:
The de novo c.916C>T (p.Arg306Cys variant in exon 2 of 2 of KCNB1 has been reported in multiple affected individuals in the available literature [PMID: 26477325.; PMID: 27652284; PMID: 29264397; PMID: 31513310; PMID: 32469098]. It is also submitted multiple times in ClinVar database by independent clinical laboratories and classified as Pathogenic/Likely Pathogenic (VarID: 449693). This variant is absent in gnomAD suggesting it is not a common benign variant in the populations represented in this database. In silico predictors suggest this variant is Pathogenic (REVEL; score: 0.86) and damaging (SIFT; score: 0). Functional studies have shown this variant in the voltage sensor domain S4, disrupts sensitivity and cooperativity of the sensor and results in loss of voltage sensing [2]. Given this evidence the de novo c.916C>T (p.Arg306Cys) variant identified in the KCNB1 gene is classified as Pathogenic.
Comment:
_x000D_ Criteria applied: PS2, PS4, PM1_SUP, PM2_SUP, PP2, PP3
Comment:
Published functional studies demonstrate a damaging effect due to exhibiting higher resting membrane potentials, higher thresholds for action potential firing, and dramatically reduced ability of repetitive firing (Saitsu et al., 2015); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29264397, 31600826, 32581362, 32954514, 32725632, 26477325, 31513310, 32469098)
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects KCNB1 function (PMID: 26477325). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNB1 protein function. ClinVar contains an entry for this variant (Variation ID: 449693). This missense change has been observed in individual(s) with early infantile epileptic encephalopathy (PMID: 26477325, 28806457, 29264397). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 306 of the KCNB1 protein (p.Arg306Cys).
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative, loss of function and gain of function are known mechanisms of disease in this gene and are associated with developmental and epileptic encephalopathy 26 (MIM#616056). However, the ultimate result of each mechanism is channel dysfunction (PMID: 31512327). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0602 - Variant is located in a cluster of pathogenic variants, S4 of the voltage-sensing domain (PMID: 26477325). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. The alternative change to a histidine has been reported once as likely pathogenic in ClinVar. (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This is a recurrent de novo variant in individuals with developmental and epileptic encephalopathy (ClinVar, PMID: 26477325, 29264397, 28806457, 31513310). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Functional studies using transfected Neuro2a cells showed that the variant disrupts sensitivity and cooperativity of the sensor (PMID: 26477325). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Whole-genome sequencing of patients with rare diseases in a national health system. | Turro E | Nature | 2020 | PMID: 32581362 |
| Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature. | Bar C | Human mutation | 2020 | PMID: 31513310 |
| Spectrum of K(V) 2.1 Dysfunction in KCNB1-Associated Neurodevelopmental Disorders. | Kang SK | Annals of neurology | 2019 | PMID: 31600826 |
| Kv2.1 voltage-gated potassium channels in developmental perspective. | Jędrychowska J | Developmental dynamics : an official publication of the American Association of Anatomists | 2019 | PMID: 31512327 |
| Clinical features and outcome of 6 new patients carrying de novo KCNB1 gene mutations. | Marini C | Neurology. Genetics | 2017 | PMID: 29264397 |
| Neurodevelopmental Disorders Caused by De Novo Variants in KCNB1 Genotypes and Phenotypes. | de Kovel CGF | JAMA neurology | 2017 | PMID: 28806457 |
| De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing. | Saitsu H | Scientific reports | 2015 | PMID: 26477325 |
Text-mined citations for rs1555889130 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.