Submissions for variant NM_001382567.1(STIM1):c.1717C>T (p.Arg573Cys)

dbSNP: rs370846246

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000636929	SCV000758375	uncertain significance	Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency; Myopathy with tubular aggregates	2023-06-20	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 530880). This variant has not been reported in the literature in individuals affected with STIM1-related conditions. This variant is present in population databases (rs370846246, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 542 of the STIM1 protein (p.Arg542Cys). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STIM1 protein function. 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.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002280882	SCV002569227	uncertain significance	Stormorken syndrome		criteria provided, single submitter	clinical testing