ClinVar Genomic variation as it relates to human health
NM_194454.3(KRIT1):c.1524_1528del (p.Arg510fs)
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.1524_1528del (p.Arg510fs)
Variation ID: 372399 Accession: VCV000372399.25
- Type and length
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Deletion, 5 bp
- Location
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Cytogenetic: 7q21.2 7: 92221937-92221941 (GRCh38) [ NCBI UCSC ] 7: 91851251-91851255 (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 Jan 9, 2017 Apr 15, 2024 Mar 31, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_194454.3:c.1524_1528del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_919436.1:p.Arg510fs frameshift NM_001013406.2:c.1380_1384del NP_001013424.1:p.Arg462fs frameshift NM_001350669.1:c.1380_1384del NP_001337598.1:p.Arg462fs frameshift NM_001350670.1:c.1380_1384del NP_001337599.1:p.Arg462fs frameshift NM_001350671.1:c.810_814del NP_001337600.1:p.Arg272fs frameshift NM_001350672.1:c.1524_1528del NP_001337601.1:p.Arg510fs frameshift NM_001350673.1:c.1524_1528del NP_001337602.1:p.Arg510fs frameshift NM_001350674.1:c.1524_1528del NP_001337603.1:p.Arg510fs frameshift NM_001350675.1:c.1524_1528del NP_001337604.1:p.Arg510fs frameshift NM_001350676.1:c.1524_1528del NP_001337605.1:p.Arg510fs frameshift NM_001350677.1:c.1524_1528del NP_001337606.1:p.Arg510fs frameshift NM_001350678.1:c.1524_1528del NP_001337607.1:p.Arg510fs frameshift NM_001350679.1:c.1524_1528del NP_001337608.1:p.Arg510fs frameshift NM_001350680.1:c.1524_1528del NP_001337609.1:p.Arg510fs frameshift NM_001350681.1:c.1524_1528del NP_001337610.1:p.Arg510fs frameshift NM_001350682.1:c.1524_1528del NP_001337611.1:p.Arg510fs frameshift NM_001350683.1:c.1524_1528del NP_001337612.1:p.Arg510fs frameshift NM_001350684.1:c.1524_1528del NP_001337613.1:p.Arg510fs frameshift NM_001350685.1:c.1524_1528del NP_001337614.1:p.Arg510fs frameshift NM_001350686.1:c.1524_1528del NP_001337615.1:p.Arg510fs frameshift NM_001350687.1:c.1524_1528del NP_001337616.1:p.Arg510fs frameshift NM_001350688.1:c.1524_1528del NP_001337617.1:p.Arg510fs frameshift NM_001350689.1:c.1524_1528del NP_001337618.1:p.Arg510fs frameshift NM_001350690.1:c.1524_1528del NP_001337619.1:p.Arg510fs frameshift NM_001350691.1:c.1524_1528del NP_001337620.1:p.Arg510fs frameshift NM_001350692.1:c.1524_1528del NP_001337621.1:p.Arg510fs frameshift NM_001350693.1:c.1524_1528del NP_001337622.1:p.Arg510fs frameshift NM_001350694.1:c.1524_1528del NP_001337623.1:p.Arg510fs frameshift NM_001350695.1:c.1524_1528del NP_001337624.1:p.Arg510fs frameshift NM_001350696.1:c.1524_1528del NP_001337625.1:p.Arg510fs frameshift NM_001350697.1:c.1524_1528del NP_001337626.1:p.Arg510fs frameshift NM_004912.4:c.1524_1528del NP_004903.2:p.Arg510fs frameshift NM_194455.1:c.1524_1528del NP_919437.1:p.Arg510fs frameshift NM_194456.1:c.1524_1528del NP_919438.1:p.Arg510fs frameshift NM_194456.1:c.1524_1528delAAGAA NC_000007.14:g.92221937_92221941del NC_000007.13:g.91851251_91851255del NG_012964.1:g.29160_29164del LRG_650:g.29160_29164del LRG_650t1:c.1524_1528del LRG_650p1:p.Arg510fs - Protein change
- R510fs, R462fs, R272fs
- Other names
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- Canonical SPDI
- NC_000007.14:92221936:TTCTT:
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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
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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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
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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
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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/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 1, 2018 | RCV000413088.20 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 31, 2022 | RCV002470851.2 |
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
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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
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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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Likely pathogenic
(Oct 31, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000852994.1
First in ClinVar: Jan 09, 2017 Last updated: Jan 09, 2017 |
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Pathogenic
(Mar 25, 2015)
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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: SCV000490588.2
First in ClinVar: Jan 09, 2017 Last updated: Jan 09, 2017 |
Comment:
The c.1524_1528delAAGAA pathogenic variant in the KRIT1 gene causes a frameshift starting with codon Arginine 510, changes this amino acid to a Cysteine residue and … (more)
The c.1524_1528delAAGAA pathogenic variant in the KRIT1 gene causes a frameshift starting with codon Arginine 510, changes this amino acid to a Cysteine residue and creates a premature Stop codon at position 8 of the new reading frame, denoted p.Arg510CysfsX8. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although this variant has not been previously reported to our knowledge, we interpret it as pathogenic. (less)
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Pathogenic
(Mar 31, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cerebral cavernous malformation
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002766787.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with cavernous malformations of CNS and retina, cerebral cavernous malformations-1 (CCM) and hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations (MIM#116860). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance. This has been reported for variants resulting in familial CCM (PMID: 16571644, OMIM). (I) 0115 - Variants in this gene are known to have variable expressivity. Intrafamilial and interfamilial variability have been reported for variants causing CCM (PMID: 29593473). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been observed in three unrelated individuals by clinical laboratories in ClinVar and in another family with cerebral cavernous malformations in the literature (PMID: 30161288). (SP) 0903 - This variant has limited evidence for segregation with disease. This variant has been observed in three affected siblings and their affected mother (PMID: 30161288). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Pathogenic
(Jan 01, 2018)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246664.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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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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A single-center study on 140 patients with cerebral cavernous malformations: 28 new pathogenic variants and functional characterization of a PDCD10 large deletion. | Nardella G | Human mutation | 2018 | PMID: 30161288 |
Cerebral Cavernous Malformations: An Update on Prevalence, Molecular Genetic Analyses, and Genetic Counselling. | Spiegler S | Molecular syndromology | 2018 | PMID: 29593473 |
Cerebral cavernous malformation: new molecular and clinical insights. | Revencu N | Journal of medical genetics | 2006 | PMID: 16571644 |
Text-mined citations for rs1057517754 ...
HelpRecord last updated Apr 15, 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.