ClinVar Genomic variation as it relates to human health
NM_194454.3(KRIT1):c.152_155del (p.Lys51fs)
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
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NM_194454.3(KRIT1):c.152_155del (p.Lys51fs)
Variation ID: 265214 Accession: VCV000265214.13
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 7q21.2 7: 92241100-92241103 (GRCh38) [ NCBI UCSC ] 7: 91870414-91870417 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Oct 10, 2016 Apr 15, 2024 Nov 4, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_194454.3:c.152_155del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_919436.1:p.Lys51fs frameshift NM_194454.3:c.152_155delAAGT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001013406.2:c.152_155del NP_001013424.1:p.Lys51fs frameshift NM_001350669.1:c.152_155del NP_001337598.1:p.Lys51fs frameshift NM_001350670.1:c.152_155del NP_001337599.1:p.Lys51fs frameshift NM_001350671.1:c.-432_-429del 5 prime UTR NM_001350672.1:c.152_155del NP_001337601.1:p.Lys51fs frameshift NM_001350673.1:c.152_155del NP_001337602.1:p.Lys51fs frameshift NM_001350674.1:c.152_155del NP_001337603.1:p.Lys51fs frameshift NM_001350675.1:c.152_155del NP_001337604.1:p.Lys51fs frameshift NM_001350676.1:c.152_155del NP_001337605.1:p.Lys51fs frameshift NM_001350677.1:c.152_155del NP_001337606.1:p.Lys51fs frameshift NM_001350678.1:c.152_155del NP_001337607.1:p.Lys51fs frameshift NM_001350679.1:c.152_155del NP_001337608.1:p.Lys51fs frameshift NM_001350680.1:c.152_155del NP_001337609.1:p.Lys51fs frameshift NM_001350681.1:c.152_155del NP_001337610.1:p.Lys51fs frameshift NM_001350682.1:c.152_155del NP_001337611.1:p.Lys51fs frameshift NM_001350683.1:c.152_155del NP_001337612.1:p.Lys51fs frameshift NM_001350684.1:c.152_155del NP_001337613.1:p.Lys51fs frameshift NM_001350685.1:c.152_155del NP_001337614.1:p.Lys51fs frameshift NM_001350686.1:c.152_155del NP_001337615.1:p.Lys51fs frameshift NM_001350687.1:c.152_155del NP_001337616.1:p.Lys51fs frameshift NM_001350688.1:c.152_155del NP_001337617.1:p.Lys51fs frameshift NM_001350689.1:c.152_155del NP_001337618.1:p.Lys51fs frameshift NM_001350690.1:c.152_155del NP_001337619.1:p.Lys51fs frameshift NM_001350691.1:c.152_155del NP_001337620.1:p.Lys51fs frameshift NM_001350692.1:c.152_155del NP_001337621.1:p.Lys51fs frameshift NM_001350693.1:c.152_155del NP_001337622.1:p.Lys51fs frameshift NM_001350694.1:c.152_155del NP_001337623.1:p.Lys51fs frameshift NM_001350695.1:c.152_155del NP_001337624.1:p.Lys51fs frameshift NM_001350696.1:c.152_155del NP_001337625.1:p.Lys51fs frameshift NM_001350697.1:c.152_155del NP_001337626.1:p.Lys51fs frameshift NM_004912.4:c.152_155del NP_004903.2:p.Lys51fs frameshift NM_194455.1:c.152_155del NP_919437.1:p.Lys51fs frameshift NM_194456.1:c.152_155del NP_919438.1:p.Lys51fs frameshift NM_194456.1:c.152_155delAAGT NC_000007.14:g.92241100_92241103del NC_000007.13:g.91870414_91870417del NG_012964.1:g.9998_10001del LRG_650:g.9998_10001del LRG_650t1:c.152_155del LRG_650p1:p.Lys51fs - Protein change
- K51fs
- Other names
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- Canonical SPDI
- NC_000007.14:92241099:ACTT:
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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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 | ||
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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
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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. |
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KRIT1 | - | - |
GRCh38 GRCh37 |
620 | 649 |
Conditions - Germline
Condition
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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
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, multiple submitters, no conflicts
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Jan 28, 2022 | RCV000255933.8 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 4, 2023 | RCV000808275.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 6, 2023 | RCV003993910.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 30, 2023 | RCV003892000.1 |
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
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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. |
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Pathogenic
(Jan 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000321810.8
First in ClinVar: Oct 10, 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; Not … (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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11161805) (less)
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Pathogenic
(Apr 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cerebral cavernous malformation
Cerebral cavernous malformation Cerebral cavernous malformation
Affected status: unknown
Allele origin:
germline
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Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV003924216.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
This variant has been reported in the literature in at least 1 individual with cerebral cavernous malformation (Sahoo 2001 PMID:11161805). This variant is not present … (more)
This variant has been reported in the literature in at least 1 individual with cerebral cavernous malformation (Sahoo 2001 PMID:11161805). This variant is not present in large control databases. This variant is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID:265214). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is a deletion of 4 nucelotides at position 152 and creates a premature stop codon 13 amino acids downstream from this location which results in an absent or abnormal protein. Loss of function variants are a known mechanism of disease for this gene (Cianfruglia 2019 PMID:30658464). In summary, this variant is classified as pathogenic based on the data above. (less)
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Pathogenic
(Nov 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cerebral cavernous malformation
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000948377.4
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Lys51Ilefs*13) in the KRIT1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Lys51Ilefs*13) in the KRIT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KRIT1 are known to be pathogenic (PMID: 10508515, 11222804, 12404106, 24689081). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with cerebral cavernous malformations (PMID: 11161805; Invitae). ClinVar contains an entry for this variant (Variation ID: 265214). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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KRIT1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000852993.2
First in ClinVar: Oct 10, 2016 Last updated: Mar 16, 2024 |
Comment:
The KRIT1 c.152_155delAAGT variant is predicted to result in a frameshift and premature protein termination (p.Lys51Ilefs*13). This variant has been reported to be causative for … (more)
The KRIT1 c.152_155delAAGT variant is predicted to result in a frameshift and premature protein termination (p.Lys51Ilefs*13). This variant has been reported to be causative for cerebral cavernous malformations (CCMs) (Sahoo et al 2001. PubMed ID: 11161805). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in KRIT1 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Jun 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cavernous hemangioma of brain
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004812729.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
This sequence change in KRIT1 is a frameshift variant predicted to cause a premature stop codon, p.(Lys51Ilefs*13), in biologically relevant exon 5/19 leading to nonsense-mediated … (more)
This sequence change in KRIT1 is a frameshift variant predicted to cause a premature stop codon, p.(Lys51Ilefs*13), in biologically relevant exon 5/19 leading to nonsense-mediated decay in a gene in which loss-of-function is an established mechanism of disease (PMID: 20301470). This variant is absent from the population database gnomAD v2.1 and v3.1.This variant has been reported in at least two individuals with KRIT1-related cerebral cavernous malformations (PMID: 11161805; ClinVar: SCV000948377.3). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM2_Supporting, PS4_Supporting (less)
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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 |
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Familial Cerebral Cavernous Malformations. | Adam MP | - | 2023 | PMID: 20301470 |
High mutation detection rates in cerebral cavernous malformation upon stringent inclusion criteria: one-third of probands are minors. | Spiegler S | Molecular genetics & genomic medicine | 2014 | PMID: 24689081 |
Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with Cerebral Cavernous Malformations. | Cavé-Riant F | European journal of human genetics : EJHG | 2002 | PMID: 12404106 |
CCM1 gene mutations in families segregating cerebral cavernous malformations. | Davenport WJ | Neurology | 2001 | PMID: 11222804 |
Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene. | Sahoo T | Genomics | 2001 | PMID: 11161805 |
Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. | Laberge-le Couteulx S | Nature genetics | 1999 | PMID: 10508515 |
Text-mined citations for rs886039400 ...
HelpRecord last updated Apr 20, 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.