ClinVar Genomic variation as it relates to human health
NM_194454.3(KRIT1):c.492A>T (p.Leu164Phe)
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_194454.3(KRIT1):c.492A>T (p.Leu164Phe)
Variation ID: 1342174 Accession: VCV001342174.2
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 7q21.2 7: 92235640 (GRCh38) [ NCBI UCSC ] 7: 91864954 (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 26, 2022 Feb 26, 2022 Sep 4, 2021 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_194454.3:c.492A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_919436.1:p.Leu164Phe missense NM_001013406.2:c.492A>T NP_001013424.1:p.Leu164Phe missense NM_001350669.1:c.492A>T NP_001337598.1:p.Leu164Phe missense NM_001350670.1:c.492A>T NP_001337599.1:p.Leu164Phe missense NM_001350671.1:c.-92A>T 5 prime UTR NM_001350672.1:c.492A>T NP_001337601.1:p.Leu164Phe missense NM_001350673.1:c.492A>T NP_001337602.1:p.Leu164Phe missense NM_001350674.1:c.492A>T NP_001337603.1:p.Leu164Phe missense NM_001350675.1:c.492A>T NP_001337604.1:p.Leu164Phe missense NM_001350676.1:c.492A>T NP_001337605.1:p.Leu164Phe missense NM_001350677.1:c.492A>T NP_001337606.1:p.Leu164Phe missense NM_001350678.1:c.492A>T NP_001337607.1:p.Leu164Phe missense NM_001350679.1:c.492A>T NP_001337608.1:p.Leu164Phe missense NM_001350680.1:c.492A>T NP_001337609.1:p.Leu164Phe missense NM_001350681.1:c.492A>T NP_001337610.1:p.Leu164Phe missense NM_001350682.1:c.492A>T NP_001337611.1:p.Leu164Phe missense NM_001350683.1:c.492A>T NP_001337612.1:p.Leu164Phe missense NM_001350684.1:c.492A>T NP_001337613.1:p.Leu164Phe missense NM_001350685.1:c.492A>T NP_001337614.1:p.Leu164Phe missense NM_001350686.1:c.492A>T NP_001337615.1:p.Leu164Phe missense NM_001350687.1:c.492A>T NP_001337616.1:p.Leu164Phe missense NM_001350688.1:c.492A>T NP_001337617.1:p.Leu164Phe missense NM_001350689.1:c.492A>T NP_001337618.1:p.Leu164Phe missense NM_001350690.1:c.492A>T NP_001337619.1:p.Leu164Phe missense NM_001350691.1:c.492A>T NP_001337620.1:p.Leu164Phe missense NM_001350692.1:c.492A>T NP_001337621.1:p.Leu164Phe missense NM_001350693.1:c.492A>T NP_001337622.1:p.Leu164Phe missense NM_001350694.1:c.492A>T NP_001337623.1:p.Leu164Phe missense NM_001350695.1:c.492A>T NP_001337624.1:p.Leu164Phe missense NM_001350696.1:c.492A>T NP_001337625.1:p.Leu164Phe missense NM_001350697.1:c.492A>T NP_001337626.1:p.Leu164Phe missense NM_004912.4:c.492A>T NP_004903.2:p.Leu164Phe missense NM_194455.1:c.492A>T NP_919437.1:p.Leu164Phe missense NM_194456.1:c.492A>T NP_919438.1:p.Leu164Phe missense NC_000007.14:g.92235640T>A NC_000007.13:g.91864954T>A NG_012964.1:g.15461A>T LRG_650:g.15461A>T LRG_650t1:c.492A>T LRG_650p1:p.Leu164Phe - Protein change
- L164F
- Other names
- p.Leu164Phe
- Canonical SPDI
- NC_000007.14:92235639:T:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- Unknown function
-
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 |
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. |
---|---|---|---|---|
Uncertain significance (1) |
criteria provided, single submitter
|
Sep 4, 2021 | RCV001838843.2 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Sep 04, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cerebral cavernous malformation
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002098375.1
First in ClinVar: Feb 26, 2022 Last updated: Feb 26, 2022 |
Comment:
A heterozygous missense variation in exon 9 of the KRIT1 gene that results in the amino acid substitution of Phenylalanine for Leucine at codon 164 … (more)
A heterozygous missense variation in exon 9 of the KRIT1 gene that results in the amino acid substitution of Phenylalanine for Leucine at codon 164 was detected. The observed variant c.492A>T (p.Leu164Phe) has not been reported in the 1000 genomes and gnomAD. The in silico prediction of the variant are possibly damaging by PolyPhen-2 (HumDiv) and damaging by LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a variant of uncertain significance. (less)
Clinical Features:
Epileptic spasm (present) , Frequent falls (present) , Inability to walk (present) , Absent speech (present)
Age: 0-9 years
Sex: male
Ethnicity/Population group: Hindu
Geographic origin: India
Method: DNA was used to perform targeted gene capture using a custom capture kit. Libraries were sequenced to mean > 80-100X coverage on the Illumina sequencing platform. Sequence obtained were aligned to human references genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication.
|
Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
---|---|---|---|---|
Unknown function
|
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002098375.1
|
|
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs2131664007 ...
HelpRecord last updated Dec 25, 2023
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.