ClinVar Miner

Submissions for variant NM_001232.4(CASQ2):c.158G>T (p.Cys53Phe)

gnomAD frequency: 0.00005  dbSNP: rs151168851
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002552490 SCV001203686 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2024-11-18 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 53 of the CASQ2 protein (p.Cys53Phe). This variant is present in population databases (rs151168851, gnomAD 0.003%). This missense change has been observed in individual(s) with catecholaminergic polymorphic ventricular tachycardia (PMID: 32693635). ClinVar contains an entry for this variant (Variation ID: 838554). Invitae Evidence 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 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 CASQ2 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.
GeneDx RCV001759739 SCV001996991 uncertain significance not provided 2019-12-18 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in a patient with CPVT who harbored an additional variant in the CASQ2 gene (Watanabe et al., 2013); This variant is associated with the following publications: (PMID: 23286974, 32693635)
Ambry Genetics RCV002400235 SCV002705713 uncertain significance Cardiovascular phenotype 2022-01-12 criteria provided, single submitter clinical testing The p.C53F variant (also known as c.158G>T), located in coding exon 1 of the CASQ2 gene, results from a G to T substitution at nucleotide position 158. The cysteine at codon 53 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration has been reported in a catecholaminergic polymorphic ventricular tachycardia (CPVT) cohort (Watanabe H et al. Heart Rhythm, 2013 Apr;10:542-7). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002489565 SCV002786832 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1; Catecholaminergic polymorphic ventricular tachycardia 2 2021-10-06 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003339437 SCV004048984 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2 2023-04-11 criteria provided, single submitter clinical testing

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