Submissions for variant NM_001382567.1(STIM1):c.1634+287G>A

gnomAD frequency: 0.00157  dbSNP: rs562406813

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000539110	SCV000634536	benign	Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency; Myopathy with tubular aggregates	2024-01-08	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001281025	SCV001468439	uncertain significance	Myopathy, tubular aggregate, 1; Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency	2021-03-30	criteria provided, single submitter	clinical testing	STIM1 NM_001277961.1 exon 11 p.Ala610Thr (c.1828G>A): This variant has been reported in the literature in 1 individual with cutaneous bruising with clinical suspicion for thrombocytopenia of unknown etiology, segregating with disease in 1 affected family member. However, both of these individuals also carried an additional variant of potential clinical significance in a different gene (GFI1B c.814+1G>A) (Johnson 2016 PMID:27479822). This variant is present in 0.2% (202/68194) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/11-4108060-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:461722). This variant amino acid Threonine (Thr) is present in several species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Computational predictive tools for this variant are limited or unavailable. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx	RCV001591217	SCV001825856	uncertain significance	not provided	2021-02-12	criteria provided, single submitter	clinical testing	In silico analysis supports that this variant does not alter splicing; Identified in two related patients with inherited thrombocytopenia, although these patients had a variant in the GFI1B gene that may have also contributed to the phenotype (Johnson et al., 2016); This variant is associated with the following publications: (PMID: 27479822)
CeGaT Center for Human Genetics Tuebingen	RCV001591217	SCV004133966	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	STIM1: BP4, BS2
PreventionGenetics, part of Exact Sciences	RCV003925620	SCV004746273	likely benign	STIM1-related disorder	2022-02-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).