ClinVar Genomic variation as it relates to human health
NM_194454.3(KRIT1):c.413T>C (p.Ile138Thr)
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.413T>C (p.Ile138Thr)
Variation ID: 449499 Accession: VCV000449499.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q21.2 7: 92236485 (GRCh38) [ NCBI UCSC ] 7: 91865799 (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 Dec 19, 2017 Feb 20, 2024 Jul 26, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_194454.3:c.413T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_919436.1:p.Ile138Thr missense NM_001013406.2:c.413T>C NP_001013424.1:p.Ile138Thr missense NM_001350669.1:c.413T>C NP_001337598.1:p.Ile138Thr missense NM_001350670.1:c.413T>C NP_001337599.1:p.Ile138Thr missense NM_001350671.1:c.-171T>C 5 prime UTR NM_001350672.1:c.413T>C NP_001337601.1:p.Ile138Thr missense NM_001350673.1:c.413T>C NP_001337602.1:p.Ile138Thr missense NM_001350674.1:c.413T>C NP_001337603.1:p.Ile138Thr missense NM_001350675.1:c.413T>C NP_001337604.1:p.Ile138Thr missense NM_001350676.1:c.413T>C NP_001337605.1:p.Ile138Thr missense NM_001350677.1:c.413T>C NP_001337606.1:p.Ile138Thr missense NM_001350678.1:c.413T>C NP_001337607.1:p.Ile138Thr missense NM_001350679.1:c.413T>C NP_001337608.1:p.Ile138Thr missense NM_001350680.1:c.413T>C NP_001337609.1:p.Ile138Thr missense NM_001350681.1:c.413T>C NP_001337610.1:p.Ile138Thr missense NM_001350682.1:c.413T>C NP_001337611.1:p.Ile138Thr missense NM_001350683.1:c.413T>C NP_001337612.1:p.Ile138Thr missense NM_001350684.1:c.413T>C NP_001337613.1:p.Ile138Thr missense NM_001350685.1:c.413T>C NP_001337614.1:p.Ile138Thr missense NM_001350686.1:c.413T>C NP_001337615.1:p.Ile138Thr missense NM_001350687.1:c.413T>C NP_001337616.1:p.Ile138Thr missense NM_001350688.1:c.413T>C NP_001337617.1:p.Ile138Thr missense NM_001350689.1:c.413T>C NP_001337618.1:p.Ile138Thr missense NM_001350690.1:c.413T>C NP_001337619.1:p.Ile138Thr missense NM_001350691.1:c.413T>C NP_001337620.1:p.Ile138Thr missense NM_001350692.1:c.413T>C NP_001337621.1:p.Ile138Thr missense NM_001350693.1:c.413T>C NP_001337622.1:p.Ile138Thr missense NM_001350694.1:c.413T>C NP_001337623.1:p.Ile138Thr missense NM_001350695.1:c.413T>C NP_001337624.1:p.Ile138Thr missense NM_001350696.1:c.413T>C NP_001337625.1:p.Ile138Thr missense NM_001350697.1:c.413T>C NP_001337626.1:p.Ile138Thr missense NM_004912.4:c.413T>C NP_004903.2:p.Ile138Thr missense NM_194455.1:c.413T>C NP_919437.1:p.Ile138Thr missense NM_194456.1:c.413T>C NP_919438.1:p.Ile138Thr missense NC_000007.14:g.92236485A>G NC_000007.13:g.91865799A>G NG_012964.1:g.14616T>C LRG_650:g.14616T>C LRG_650t1:c.413T>C LRG_650p1:p.Ile138Thr - Protein change
- I138T
- Other names
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- Canonical SPDI
- NC_000007.14:92236484:A:G
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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
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
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
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. |
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KRIT1 | - | - |
GRCh38 GRCh37 |
613 | 642 |
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. |
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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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May 20, 2021 | RCV000524002.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 26, 2022 | RCV001046152.7 |
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. |
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Uncertain significance
(May 20, 2021)
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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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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501377.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
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Uncertain significance
(Dec 22, 2020)
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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: SCV000617708.4
First in ClinVar: Dec 19, 2017 Last updated: Mar 04, 2023 |
Comment:
Observed in an individual with a single cerebral cavernous malformation lesion and their asymptomatic father who had a normal brain MRI (D'Angelo et al., 2011); … (more)
Observed in an individual with a single cerebral cavernous malformation lesion and their asymptomatic father who had a normal brain MRI (D'Angelo et al., 2011); Published functional studies demonstrate an effect on splicing (D'Angelo et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21029238) (less)
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Uncertain significance
(Jul 26, 2022)
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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: SCV001210041.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 20, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 449499). This missense change has been observed in individual(s) with clinical features of cerebral cavernous malformation (PMID: 21029238). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 138 of the KRIT1 protein (p.Ile138Thr). (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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Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation. | D'Angelo R | Brain pathology (Zurich, Switzerland) | 2011 | PMID: 21029238 |
Text-mined citations for rs1172939308 ...
HelpRecord last updated Feb 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.