NM_001382567.1(STIM1):c.239A>C (p.Asn80Thr) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 3, 2019
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:: RCV001068304.8

Allele description [Variation Report for NM_001382567.1(STIM1):c.239A>C (p.Asn80Thr)]

NM_001382567.1(STIM1):c.239A>C (p.Asn80Thr)

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.239A>C (p.Asn80Thr)

HGVS:

NC_000011.10:g.3967651A>C
NG_016277.1:g.116949A>C
NM_001277961.3:c.239A>C
NM_001277962.2:c.239A>C
NM_001382566.1:c.17A>C
NM_001382567.1:c.239A>CMANE SELECT
NM_001382568.1:c.239A>C
NM_001382569.1:c.136-56222A>C
NM_001382570.1:c.239A>C
NM_001382571.1:c.-98-56222A>C
NM_001382572.1:c.239A>C
NM_001382573.1:c.17A>C
NM_001382574.1:c.17A>C
NM_001382575.1:c.17A>C
NM_001382576.1:c.17A>C
NM_001382577.1:c.17A>C
NM_001382578.1:c.17A>C
NM_001382579.1:c.17A>C
NM_001382580.1:c.-219-56222A>C
NM_001382581.1:c.-219-56222A>C
NM_003156.4:c.239A>C
NP_001264890.1:p.Asn80Thr
NP_001264891.1:p.Asn80Thr
NP_001369495.1:p.Asn6Thr
NP_001369496.1:p.Asn80Thr
NP_001369497.1:p.Asn80Thr
NP_001369499.1:p.Asn80Thr
NP_001369501.1:p.Asn80Thr
NP_001369502.1:p.Asn6Thr
NP_001369503.1:p.Asn6Thr
NP_001369504.1:p.Asn6Thr
NP_001369505.1:p.Asn6Thr
NP_001369506.1:p.Asn6Thr
NP_001369507.1:p.Asn6Thr
NP_001369508.1:p.Asn6Thr
NP_003147.2:p.Asn80Thr
NP_003147.2:p.Asn80Thr
LRG_164t1:c.239A>C
LRG_164:g.116949A>C
LRG_164p1:p.Asn80Thr
NC_000011.9:g.3988881A>C
NM_003156.3:c.239A>C
NR_168436.1:n.846A>C
NR_168437.1:n.846A>C
NR_168438.1:n.846A>C
Q13586:p.Asn80Thr

Protein change:

N6T; ASN80THR

Links:

UniProtKB: Q13586#VAR_075619; OMIM: 605921.0010; dbSNP: rs748277951

NCBI 1000 Genomes Browser:

rs748277951

Molecular consequence:

NM_001382569.1:c.136-56222A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001382571.1:c.-98-56222A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001382580.1:c.-219-56222A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001382581.1:c.-219-56222A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001277961.3:c.239A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001277962.2:c.239A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382566.1:c.17A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382567.1:c.239A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382568.1:c.239A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382570.1:c.239A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382572.1:c.239A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382573.1:c.17A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382574.1:c.17A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382575.1:c.17A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382576.1:c.17A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382577.1:c.17A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382578.1:c.17A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382579.1:c.17A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003156.4:c.239A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_168436.1:n.846A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_168437.1:n.846A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_168438.1:n.846A>C - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001233408	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 3, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001233408

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 3, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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 Invitae, SCV001233408.5

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has been reported to affect STIM1 protein function (PMID:¬†25326555). This variant has been observed in individuals affected with tubular aggregate myopathy (TAM) and was observed¬†to be de novo in one individual¬†(PMID:¬†25326555). ClinVar contains an entry for this variant (Variation ID: 189363). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with threonine at codon 80 of the STIM1 protein (p.Asn80Thr). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and threonine.

#	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: Jun 23, 2024

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