ClinVar Genomic variation as it relates to human health
NM_001382567.1(STIM1):c.343A>T (p.Ile115Phe)
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_001382567.1(STIM1):c.343A>T (p.Ile115Phe)
Variation ID: 143191 Accession: VCV000143191.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p15.4 11: 4023945 (GRCh38) [ NCBI UCSC ] 11: 4045175 (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 Aug 10, 2014 Feb 28, 2024 Apr 6, 2020 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001382567.1:c.343A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001369496.1:p.Ile115Phe missense NM_001277961.3:c.343A>T NP_001264890.1:p.Ile115Phe missense NM_001277962.2:c.343A>T NP_001264891.1:p.Ile115Phe missense NM_001382566.1:c.121A>T NP_001369495.1:p.Ile41Phe missense NM_001382568.1:c.343A>T NP_001369497.1:p.Ile115Phe missense NM_001382569.1:c.208A>T NP_001369498.1:p.Ile70Phe missense NM_001382570.1:c.343A>T NP_001369499.1:p.Ile115Phe missense NM_001382571.1:c.-26A>T 5 prime UTR NM_001382572.1:c.343A>T NP_001369501.1:p.Ile115Phe missense NM_001382573.1:c.121A>T NP_001369502.1:p.Ile41Phe missense NM_001382574.1:c.121A>T NP_001369503.1:p.Ile41Phe missense NM_001382575.1:c.121A>T NP_001369504.1:p.Ile41Phe missense NM_001382576.1:c.121A>T NP_001369505.1:p.Ile41Phe missense NM_001382577.1:c.121A>T NP_001369506.1:p.Ile41Phe missense NM_001382578.1:c.121A>T NP_001369507.1:p.Ile41Phe missense NM_001382579.1:c.121A>T NP_001369508.1:p.Ile41Phe missense NM_001382580.1:c.-147A>T 5 prime UTR NM_001382581.1:c.-147A>T 5 prime UTR NM_003156.4:c.343A>T NP_003147.2:p.Ile115Phe missense NR_168436.1:n.950A>T non-coding transcript variant NR_168437.1:n.950A>T non-coding transcript variant NR_168438.1:n.950A>T non-coding transcript variant NC_000011.10:g.4023945A>T NC_000011.9:g.4045175A>T NG_016277.1:g.173243A>T LRG_164:g.173243A>T LRG_164t1:c.343A>T LRG_164p1:p.Ile115Phe Q13586:p.Ile115Phe - Protein change
- I115F, I41F, I70F
- Other names
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- Canonical SPDI
- NC_000011.10:4023944:A:T
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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
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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
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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STIM1 | - | - |
GRCh38 GRCh37 |
620 | 755 |
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 (1) |
no assertion criteria provided
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- | RCV000132725.1 | |
Pathogenic (1) |
no assertion criteria provided
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Mar 1, 2015 | RCV000144069.6 | |
Pathogenic (1) |
no assertion criteria provided
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Mar 1, 2015 | RCV000169763.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 6, 2020 | RCV000537798.9 |
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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Pathogenic
(Apr 06, 2020)
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criteria provided, single submitter
Method: clinical testing
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Myopathy with tubular aggregates
Combined immunodeficiency due to STIM1 deficiency Stormorken syndrome
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000634524.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function do … (more)
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant has been reported to be de novo in individuals affected with tubular aggregate myopathy and York platelet syndrome (YPS) and segregates in a family affected with YPS (PMID: 24570283, 25577287). ClinVar contains an entry for this variant (Variation ID: 143191). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with phenylalanine at codon 115 of the STIM1 protein (p.Ile115Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. (less)
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Pathogenic
(Mar 01, 2015)
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no assertion criteria provided
Method: literature only
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MYOPATHY, TUBULAR AGGREGATE, 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000189141.5
First in ClinVar: Sep 22, 2014 Last updated: Dec 15, 2018 |
Comment on evidence:
Tubular Aggregate Myopathy 1 In a Caucasian girl with tubular aggregate myopathy-1 (TAM1; 160565), Hedberg et al. (2014) identified a de novo heterozygous c.343A-T transversion … (more)
Tubular Aggregate Myopathy 1 In a Caucasian girl with tubular aggregate myopathy-1 (TAM1; 160565), Hedberg et al. (2014) identified a de novo heterozygous c.343A-T transversion in the STIM1 gene, resulting in an ile115-to-phe (I115F) substitution in the EF hand domain. The mutation was not found in the Exome Variant Server database or in 200 control chromosomes. Functional studies of the variant were not performed. Stormorken Syndrome In 3 affected members of a family with Stormorken syndrome (STRMK; 185070), Markello et al. (2015) identified a heterozygous I115F mutation in the STIM1 gene. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In an unrelated patient with STRMK, Markello et al. (2015) also found the I115F mutation, which occurred de novo; this patient had no family history. Functional studies of the variant were not performed, but Markello et al. (2015) noted that the mutation occurs at a highly conserved residue in the EF2-hand domain, which may alter calcium binding and responses, resulting in a gain of function. One of the families (family A) had previously been reported in detail by White (2003, 2003) and White and Ahlstrand (2003, 2003). (less)
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Pathogenic
(Mar 01, 2015)
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no assertion criteria provided
Method: literature only
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STORMORKEN SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000221327.4
First in ClinVar: Apr 11, 2015 Last updated: Dec 15, 2018 |
Comment on evidence:
Tubular Aggregate Myopathy 1 In a Caucasian girl with tubular aggregate myopathy-1 (TAM1; 160565), Hedberg et al. (2014) identified a de novo heterozygous c.343A-T transversion … (more)
Tubular Aggregate Myopathy 1 In a Caucasian girl with tubular aggregate myopathy-1 (TAM1; 160565), Hedberg et al. (2014) identified a de novo heterozygous c.343A-T transversion in the STIM1 gene, resulting in an ile115-to-phe (I115F) substitution in the EF hand domain. The mutation was not found in the Exome Variant Server database or in 200 control chromosomes. Functional studies of the variant were not performed. Stormorken Syndrome In 3 affected members of a family with Stormorken syndrome (STRMK; 185070), Markello et al. (2015) identified a heterozygous I115F mutation in the STIM1 gene. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In an unrelated patient with STRMK, Markello et al. (2015) also found the I115F mutation, which occurred de novo; this patient had no family history. Functional studies of the variant were not performed, but Markello et al. (2015) noted that the mutation occurs at a highly conserved residue in the EF2-hand domain, which may alter calcium binding and responses, resulting in a gain of function. One of the families (family A) had previously been reported in detail by White (2003, 2003) and White and Ahlstrand (2003, 2003). (less)
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pathogenic
(-)
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no assertion criteria provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
unknown
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Undiagnosed Diseases Program Translational Research Laboratory, National Institutes of Health
Accession: SCV000187654.1
First in ClinVar: Aug 10, 2014 Last updated: Aug 10, 2014 |
Comment:
Converted during submission to Pathogenic.
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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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York platelet syndrome is a CRAC channelopathy due to gain-of-function mutations in STIM1. | Markello T | Molecular genetics and metabolism | 2015 | PMID: 25577287 |
Childhood onset tubular aggregate myopathy associated with de novo STIM1 mutations. | Hedberg C | Journal of neurology | 2014 | PMID: 24570283 |
Giant electron dense chains, clusters and granules in megakaryocytes and platelets with normal dense bodies: an inherited thrombocytopenic disorder IV. Ultrastructural cytochemistry and analytical electron microscopy. | White JG | Platelets | 2003 | PMID: 12944248 |
Giant electron dense chains, clusters and granules in megakaryocytes and platelets with normal dense bodies: an inherited thrombocytopenic disorder III. Platelet analytical electron microscopy. | White JG | Platelets | 2003 | PMID: 12944247 |
Giant electron-dense chains, clusters and granules in megakaryocytes and platelets with normal dense bodies: an inherited thrombocytopenic disorder. | White JG | Platelets | 2003 | PMID: 12745453 |
Giant electron-dense chains, clusters and granules in megakaryocytes and platelets with normal dense bodies: an inherited thrombocytopenic disorder I. Megakaryocytes. | White JG | Platelets | 2003 | PMID: 12623447 |
Text-mined citations for rs527236030 ...
HelpRecord last updated Mar 05, 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.