Submissions for variant NM_001382567.1(STIM1):c.932G>A (p.Arg311Gln)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002737058	SCV003572395	uncertain significance	Inborn genetic diseases	2021-07-20	criteria provided, single submitter	clinical testing	The c.932G>A (p.R311Q) alteration is located in exon 7 (coding exon 7) of the STIM1 gene. This alteration results from a G to A substitution at nucleotide position 932, causing the arginine (R) at amino acid position 311 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003777694	SCV004571080	uncertain significance	Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency; Myopathy with tubular aggregates	2023-08-03	criteria provided, single submitter	clinical testing	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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on STIM1 protein function. ClinVar contains an entry for this variant (Variation ID: 2238467). This variant has not been reported in the literature in individuals affected with STIM1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 311 of the STIM1 protein (p.Arg311Gln).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004783032	SCV005394713	uncertain significance	not specified	2024-09-24	criteria provided, single submitter	clinical testing	Variant summary: STIM1 c.932G>A (p.Arg311Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.1e-05 in 194620 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.932G>A in individuals affected with STIM1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2238467). Based on the evidence outlined above, the variant was classified as uncertain significance.