ClinVar Genomic variation as it relates to human health
NM_007059.4(KPTN):c.597_598dup (p.Ser200fs)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007059.4(KPTN):c.597_598dup (p.Ser200fs)
Variation ID: 279826 Accession: VCV000279826.28
- Type and length
-
Duplication, 2 bp
- Location
-
Cytogenetic: 19q13.32 19: 47480760-47480761 (GRCh38) [ NCBI UCSC ] 19: 47984017-47984018 (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 6, 2016 May 12, 2024 Jul 1, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_007059.4:c.597_598dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_008990.2:p.Ser200fs frameshift NM_007059.4:c.598_599insTA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001291296.2:c.429_430dup NP_001278225.1:p.Ser144fs frameshift NM_007059.3:c.597_598dup NC_000019.10:g.47480761_47480762dup NC_000019.9:g.47984018_47984019dup NG_034097.1:g.8503_8504dup - Protein change
- S200fs, S144fs
- Other names
- -
- Canonical SPDI
- NC_000019.10:47480760:TA:TATA
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00009
The Genome Aggregation Database (gnomAD) 0.00010
Trans-Omics for Precision Medicine (TOPMed) 0.00010
The Genome Aggregation Database (gnomAD), exomes 0.00011
Exome Aggregation Consortium (ExAC) 0.00012
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. |
|||
KPTN | - | - |
GRCh38 GRCh37 |
158 | 178 |
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, multiple submitters, no conflicts
|
Jul 1, 2023 | RCV000307812.21 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Jul 15, 2022 | RCV000652012.11 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Apr 7, 2020 | RCV001263307.3 |
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
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Macrocephaly-developmental delay syndrome
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001141109.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
Pathogenic
(Dec 11, 2019)
|
criteria provided, single submitter
Method: research
|
Macrocephaly-developmental delay syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
|
Cavalleri Lab, Royal College of Surgeons in Ireland
Accession: SCV001160803.1
First in ClinVar: Apr 15, 2020 Last updated: Apr 15, 2020 |
Comment:
ACMG evidence PVS1, PM3, PP3
|
|
Likely pathogenic
(Apr 07, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Intellectual disability
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
New York Genome Center
Study: CSER-NYCKidSeq
Accession: SCV001441348.1 First in ClinVar: Nov 06, 2020 Last updated: Nov 06, 2020 |
Secondary finding: no
|
|
Pathogenic
(Apr 21, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000329381.5
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26633542, 31999056, 31980526, 32238909, 32808430) (less)
|
|
Pathogenic
(Jul 15, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Macrocephaly-developmental delay syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000773871.7
First in ClinVar: May 28, 2018 Last updated: Feb 20, 2024 |
Comment:
This variant has not been reported in the literature in individuals affected with KPTN-related conditions. For these reasons, this variant has been classified as Pathogenic. … (more)
This variant has not been reported in the literature in individuals affected with KPTN-related conditions. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 279826). This variant is present in population databases (rs766372684, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Ser200Ilefs*55) in the KPTN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KPTN are known to be pathogenic (PMID: 24239382, 25847626). (less)
|
|
Pathogenic
(Jul 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001747927.15
First in ClinVar: Jul 10, 2021 Last updated: May 12, 2024 |
Comment:
KPTN: PVS1, PM2, PM3:Supporting
Number of individuals with the variant: 4
|
|
Pathogenic
(Apr 07, 2023)
|
no assertion criteria provided
Method: literature only
|
INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 41
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV003853605.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
Comment on evidence:
In 2 Spanish sibs with autosomal recessive intellectual developmental disorder-41 (MRT41; 615637), Pacio Miguez et al. (2020) identified homozygosity for a 2-bp duplication (c.597_598dup, NM_007059.3) … (more)
In 2 Spanish sibs with autosomal recessive intellectual developmental disorder-41 (MRT41; 615637), Pacio Miguez et al. (2020) identified homozygosity for a 2-bp duplication (c.597_598dup, NM_007059.3) in the KPTN gene, resulting in a frameshift and premature termination (Ser200IlefsTer55). The variant was present in the gnomAD database at an allele frequency of 0.000103. No segregation information was provided, and no functional studies were performed. (less)
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Pathogenic variants in KPTN, a rare cause of macrocephaly and intellectual disability. | Pacio Miguez M | American journal of medical genetics. Part A | 2020 | PMID: 32808430 |
A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability. | Benson KA | European journal of human genetics : EJHG | 2020 | PMID: 32238909 |
Novel homozygous mutation in KPTN gene causing a familial intellectual disability-macrocephaly syndrome. | Pajusalu S | American journal of medical genetics. Part A | 2015 | PMID: 25847626 |
Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures. | Baple EL | American journal of human genetics | 2014 | PMID: 24239382 |
Text-mined citations for rs766372684 ...
HelpRecord last updated May 19, 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.