ClinVar Genomic variation as it relates to human health
NM_001382567.1(STIM1):c.252T>A (p.Asp84Glu)
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.252T>A (p.Asp84Glu)
Variation ID: 3236678 Accession: VCV003236678.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p15.4 11: 3967664 (GRCh38) [ NCBI UCSC ] 11: 3988894 (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 May 27, 2024 May 26, 2024 May 22, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001382567.1:c.252T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001369496.1:p.Asp84Glu missense NM_001277961.3:c.252T>A NP_001264890.1:p.Asp84Glu missense NM_001277962.2:c.252T>A NP_001264891.1:p.Asp84Glu missense NM_001382566.1:c.30T>A NP_001369495.1:p.Asp10Glu missense NM_001382568.1:c.252T>A NP_001369497.1:p.Asp84Glu missense NM_001382569.1:c.136-56209T>A intron variant NM_001382570.1:c.252T>A NP_001369499.1:p.Asp84Glu missense NM_001382571.1:c.-98-56209T>A intron variant NM_001382572.1:c.252T>A NP_001369501.1:p.Asp84Glu missense NM_001382573.1:c.30T>A NP_001369502.1:p.Asp10Glu missense NM_001382574.1:c.30T>A NP_001369503.1:p.Asp10Glu missense NM_001382575.1:c.30T>A NP_001369504.1:p.Asp10Glu missense NM_001382576.1:c.30T>A NP_001369505.1:p.Asp10Glu missense NM_001382577.1:c.30T>A NP_001369506.1:p.Asp10Glu missense NM_001382578.1:c.30T>A NP_001369507.1:p.Asp10Glu missense NM_001382579.1:c.30T>A NP_001369508.1:p.Asp10Glu missense NM_001382580.1:c.-219-56209T>A intron variant NM_001382581.1:c.-219-56209T>A intron variant NM_003156.4:c.252T>A NP_003147.2:p.Asp84Glu missense NR_168436.1:n.859T>A non-coding transcript variant NR_168437.1:n.859T>A non-coding transcript variant NR_168438.1:n.859T>A non-coding transcript variant NC_000011.10:g.3967664T>A NC_000011.9:g.3988894T>A NG_016277.1:g.116962T>A LRG_164:g.116962T>A LRG_164t1:c.252T>A LRG_164p1:p.Asp84Glu - Protein change
- D10E, D84E
- Other names
- NR_168438.1:n.859T>A
- Canonical SPDI
- NC_000011.10:3967663:T:A
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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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- Links
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
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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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STIM1 | - | - |
GRCh38 GRCh37 |
635 | 771 |
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
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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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Likely pathogenic (1) |
criteria provided, single submitter
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May 22, 2024 | RCV004556138.1 |
Submissions - Germline
Classification
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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
(May 22, 2024)
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criteria provided, single submitter
Method: curation
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Myopathy, tubular aggregate, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV005045269.1
First in ClinVar: May 26, 2024 Last updated: May 26, 2024 |
Comment:
The heterozygous p.Asp84Glu variant in STIM1 was identified by our study in one individual with myopathy, tubular aggregate, 1. This variant has been reported in … (more)
The heterozygous p.Asp84Glu variant in STIM1 was identified by our study in one individual with myopathy, tubular aggregate, 1. This variant has been reported in 2 individuals with tubular aggregate myopathy (PMIDs: 34368974, 27876257), and was absent from large population studies. This variant was found to be de novo in one individual without confirmed paternity and maternity (PMID: 34368974). The number of reported affected individuals with this variant is slightly greater than expected compared to non-affected individuals with this variant. In vitro functional studies provide some evidence that the p.Asp84Glu variant may impact protein function (PMID: 27876257). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. One additional pathogenic variant, resulting in a different amino acid change at the same position, (p.Asp84Gly), has been reported in association with disease in ClinVar, supporting that a change at this position may not be tolerated (Variation ID: 41481). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal dominant myopathy, tubular aggregate, 1. ACMG/AMP Criteria applied: PS4_Supporting, PM2_Supporting, PS3_Moderate, PM5 (Richards 2015). (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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Tubular aggregate myopathy with features of Stormorken disease due to a new STIM1 mutation. | Noury JB | Neuromuscular disorders : NMD | 2017 | PMID: 27876257 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d96167b8-2284-40bc-8601-6b41c6bdc680 | - | - | - | - |
Text-mined citations for this variant ...
HelpRecord last updated Jun 02, 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.