Submissions for variant NM_001382567.1(STIM1):c.1634+319G>A

gnomAD frequency: 0.00808  dbSNP: rs118128831

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768100	SCV000899003	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 exon 11 c.1859+1G>A: This variant has been reported in the literature as heterozygous in at least 4 individuals with Common Variable Immunodeficiency Disorders (CVIDs) (van Schouwenberg 2015 PMID:26122175). However, this variant is present in 2% (63/3166) of European alleles, including 1 homozygote in the Exome Aggregation Database (http://exac.broadinstitute.org/rs118128831). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. However, there is insufficient evidence to determine loss of function (LOF) as an established disease mechanism for this gene. Further studies are needed to understand its impact. In summary, data on this variant is conflicting and insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001512196	SCV001719566	benign	Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency; Myopathy with tubular aggregates	2024-01-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001672952	SCV001882349	benign	not provided	2020-07-16	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26122175)
CeGaT Center for Human Genetics Tuebingen	RCV001672952	SCV002544535	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	STIM1: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003918253	SCV004733848	likely benign	STIM1-related disorder	2019-12-03	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).