NM_001382567.1(STIM1):c.1270C>T (p.Arg424Trp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 7, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002015883.6

Allele description [Variation Report for NM_001382567.1(STIM1):c.1270C>T (p.Arg424Trp)]

NM_001382567.1(STIM1):c.1270C>T (p.Arg424Trp)

Gene:

STIM1:stromal interaction molecule 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_001382567.1(STIM1):c.1270C>T (p.Arg424Trp)

HGVS:

NC_000011.10:g.4083294C>T
NG_016277.1:g.232592C>T
NM_001277961.3:c.1270C>T
NM_001277962.2:c.1270C>T
NM_001382566.1:c.1048C>T
NM_001382567.1:c.1270C>TMANE SELECT
NM_001382568.1:c.1291C>T
NM_001382569.1:c.1135C>T
NM_001382570.1:c.1042C>T
NM_001382571.1:c.790C>T
NM_001382573.1:c.1048C>T
NM_001382575.1:c.1048C>T
NM_001382576.1:c.1048C>T
NM_001382577.1:c.1048C>T
NM_001382578.1:c.1048C>T
NM_001382579.1:c.1048C>T
NM_001382580.1:c.781C>T
NM_001382581.1:c.781C>T
NM_003156.4:c.1270C>T
NP_001264890.1:p.Arg424Trp
NP_001264891.1:p.Arg424Trp
NP_001369495.1:p.Arg350Trp
NP_001369496.1:p.Arg424Trp
NP_001369497.1:p.Arg431Trp
NP_001369498.1:p.Arg379Trp
NP_001369499.1:p.Arg348Trp
NP_001369500.1:p.Arg264Trp
NP_001369502.1:p.Arg350Trp
NP_001369504.1:p.Arg350Trp
NP_001369505.1:p.Arg350Trp
NP_001369506.1:p.Arg350Trp
NP_001369507.1:p.Arg350Trp
NP_001369508.1:p.Arg350Trp
NP_001369509.1:p.Arg261Trp
NP_001369510.1:p.Arg261Trp
NP_003147.2:p.Arg424Trp
LRG_164:g.232592C>T
NC_000011.9:g.4104524C>T
NR_168437.1:n.1699C>T
NR_168438.1:n.1521C>T

Protein change:

R261W

Links:

dbSNP: rs200892145

NCBI 1000 Genomes Browser:

rs200892145

Molecular consequence:

NM_001277961.3:c.1270C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001277962.2:c.1270C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382566.1:c.1048C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382567.1:c.1270C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382568.1:c.1291C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382569.1:c.1135C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382570.1:c.1042C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382571.1:c.790C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382573.1:c.1048C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382575.1:c.1048C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382576.1:c.1048C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382577.1:c.1048C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382578.1:c.1048C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382579.1:c.1048C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382580.1:c.781C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382581.1:c.781C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003156.4:c.1270C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_168437.1:n.1699C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_168438.1:n.1521C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Stormorken syndrome (STRMK)
Synonyms:: THROMBOCYTOPATHY, ASPLENIA, AND MIOSIS
Identifiers:: MONDO: MONDO:0008497; MedGen: C1861451; Orphanet: 3204; OMIM: 185070

Name:: Combined immunodeficiency due to STIM1 deficiency
Synonyms:: Immune dysfunction with T-cell inactivation due to calcium entry defect 2; STIM1 DEFICIENCY; IMMUNODEFICIENCY 10
Identifiers:: MONDO: MONDO:0013008; MedGen: C2748557; Orphanet: 169090; Orphanet: 317430; OMIM: 612783

Name:: Myopathy with tubular aggregates (TAM)
Synonyms:: Tubular Aggregate Myopathy
Identifiers:: MONDO: MONDO:0008051; MedGen: C0410207; OMIM: PS160565

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002288911	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 7, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32098964, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002288911

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 7, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Optogenetic engineering to probe the molecular choreography of STIM1-mediated cell signaling.

Ma G, He L, Liu S, Xie J, Huang Z, Jing J, Lee YT, Wang R, Luo H, Han W, Huang Y, Zhou Y.

Nat Commun. 2020 Feb 25;11(1):1039. doi: 10.1038/s41467-020-14841-9.

PubMed [citation]

PMID:: 32098964
PMCID:: PMC7042325

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002288911.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Experimental studies have shown that this missense change affects STIM1 function (PMID: 32098964). 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: 1500742). This variant has not been reported in the literature in individuals affected with STIM1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0008%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 424 of the STIM1 protein (p.Arg424Trp).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine