ClinVar Miner

Submissions for variant NM_001382567.1(STIM1):c.454G>A (p.Glu152Lys)

gnomAD frequency: 0.00013  dbSNP: rs143916878
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000690569 SCV000818259 uncertain significance Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency; Myopathy with tubular aggregates 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 152 of the STIM1 protein (p.Glu152Lys). This variant is present in population databases (rs143916878, gnomAD 0.06%). This missense change has been observed in individual(s) with chronic pancreatitis (PMID: 33468626). ClinVar contains an entry for this variant (Variation ID: 569843). 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. Experimental studies have shown that this missense change affects STIM1 function (PMID: 33468626). 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.
GeneDx RCV003163149 SCV003915292 uncertain significance not provided 2022-10-04 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect, as the E152K variant in the heterozygous form deregulates Ca2+ signaling, increasing cytotoxicity in transfected cells (Burgos et al., 2021); Has not been previously published as pathogenic or benign in association with neuromuscular disorders to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33468626)
Fulgent Genetics, Fulgent Genetics RCV005046931 SCV005683527 uncertain significance Myopathy, tubular aggregate, 1; Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency 2024-01-17 criteria provided, single submitter clinical testing

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