ClinVar Miner

Submissions for variant NM_001232.4(CASQ2):c.83A>G (p.Tyr28Cys)

gnomAD frequency: 0.00001  dbSNP: rs1230753325
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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 RCV002554403 SCV001222087 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2022-08-15 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 28 of the CASQ2 protein (p.Tyr28Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CASQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 852876). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics, Fulgent Genetics RCV002489651 SCV002793245 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1; Catecholaminergic polymorphic ventricular tachycardia 2 2021-11-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV003307885 SCV004001934 uncertain significance Cardiovascular phenotype 2023-04-13 criteria provided, single submitter clinical testing The p.Y28C variant (also known as c.83A>G), located in coding exon 1 of the CASQ2 gene, results from an A to G substitution at nucleotide position 83. The tyrosine at codon 28 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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.
Genome-Nilou Lab RCV003339449 SCV004048995 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2 2023-04-11 criteria provided, single submitter clinical testing
Molecular Genetics, Royal Melbourne Hospital RCV003994203 SCV004812845 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2023-07-07 criteria provided, single submitter clinical testing This sequence change in CASQ2 is predicted to replace tyrosine with cysteine at codon 28, p.(Tyr28Cys). The tyrosine residue is highly conserved (100 vertebrates, UCSC), and is not located in an annotated domain. There is a large physicochemical difference between tyrosine and cysteine. This variant is present in a single European (non-Finnish) individual in the population database gnomAD v3.1 (1/68,032 alleles). To our knowledge, this variant has not been previously reported in the relevant scientific literature. Computational evidence predicts a deleterious effect for the missense substitution (REVEL = 0.692). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting, PP3.

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