For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with KRIT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile325Hisfs*11) 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).
ClinVar Genomic variation as it relates to human health
NM_194454.3(KRIT1):c.972dup (p.Ile325fs)
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.
(1)
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
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_194454.3(KRIT1):c.972dup (p.Ile325fs)
Variation ID: 2717742 Accession: VCV002717742.1
- Type and length
-
Duplication, 1 bp
- Location
-
Cytogenetic: 7q21.2 7: 92234465-92234466 (GRCh38) [ NCBI UCSC ] 7: 91863779-91863780 (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 Feb 14, 2024 Feb 14, 2024 Jun 16, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_194454.3:c.972dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_919436.1:p.Ile325fs frameshift NM_001013406.2:c.845+342dup intron variant NM_001350669.1:c.845+342dup intron variant NM_001350670.1:c.845+342dup intron variant NM_001350671.1:c.258dup NP_001337600.1:p.Ile87fs frameshift NM_001350672.1:c.972dup NP_001337601.1:p.Ile325fs frameshift NM_001350673.1:c.972dup NP_001337602.1:p.Ile325fs frameshift NM_001350674.1:c.972dup NP_001337603.1:p.Ile325fs frameshift NM_001350675.1:c.972dup NP_001337604.1:p.Ile325fs frameshift NM_001350676.1:c.972dup NP_001337605.1:p.Ile325fs frameshift NM_001350677.1:c.972dup NP_001337606.1:p.Ile325fs frameshift NM_001350678.1:c.972dup NP_001337607.1:p.Ile325fs frameshift NM_001350679.1:c.972dup NP_001337608.1:p.Ile325fs frameshift NM_001350680.1:c.972dup NP_001337609.1:p.Ile325fs frameshift NM_001350681.1:c.972dup NP_001337610.1:p.Ile325fs frameshift NM_001350682.1:c.972dup NP_001337611.1:p.Ile325fs frameshift NM_001350683.1:c.972dup NP_001337612.1:p.Ile325fs frameshift NM_001350684.1:c.972dup NP_001337613.1:p.Ile325fs frameshift NM_001350685.1:c.972dup NP_001337614.1:p.Ile325fs frameshift NM_001350686.1:c.972dup NP_001337615.1:p.Ile325fs frameshift NM_001350687.1:c.972dup NP_001337616.1:p.Ile325fs frameshift NM_001350688.1:c.972dup NP_001337617.1:p.Ile325fs frameshift NM_001350689.1:c.972dup NP_001337618.1:p.Ile325fs frameshift NM_001350690.1:c.972dup NP_001337619.1:p.Ile325fs frameshift NM_001350691.1:c.972dup NP_001337620.1:p.Ile325fs frameshift NM_001350692.1:c.972dup NP_001337621.1:p.Ile325fs frameshift NM_001350693.1:c.972dup NP_001337622.1:p.Ile325fs frameshift NM_001350694.1:c.972dup NP_001337623.1:p.Ile325fs frameshift NM_001350695.1:c.972dup NP_001337624.1:p.Ile325fs frameshift NM_001350696.1:c.972dup NP_001337625.1:p.Ile325fs frameshift NM_001350697.1:c.972dup NP_001337626.1:p.Ile325fs frameshift NM_004912.4:c.972dup NP_004903.2:p.Ile325fs frameshift NM_194455.1:c.972dup NP_919437.1:p.Ile325fs frameshift NM_194456.1:c.972dup NP_919438.1:p.Ile325fs frameshift NC_000007.14:g.92234468dup NC_000007.13:g.91863782dup NG_012964.1:g.16635dup LRG_650:g.16635dup LRG_650t1:c.972dup LRG_650p1:p.Ile325fs - Protein change
- I325fs, I87fs
- Other names
- -
- Canonical SPDI
- NC_000007.14:92234465:GGG:GGGG
-
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.
- -
- 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. |
|||
| KRIT1 | - | - |
GRCh38 GRCh37 |
651 | 681 | |
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 (1) |
criteria provided, single submitter
|
Jun 16, 2023 | RCV003522230.2 |
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
(Jun 16, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Cerebral cavernous malformation
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004272895.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with KRIT1-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with KRIT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile325Hisfs*11) 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). (less)
|
Comment:
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. |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with KRIT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile325Hisfs*11) 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).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. | Laberge-le Couteulx S | Nature genetics | 1999 | PMID: 10508515 |
Text-mined citations for this variant ...
HelpRecord last updated Sep 30, 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.