Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000222224 | SCV000270019 | likely benign | not specified | 2015-02-05 | criteria provided, single submitter | clinical testing | p.His244Tyr in exon 6 of CASQ2: This variant is not expected to have clinical si gnificance because it has been identified in 0.3% (25/9422) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs142036299). |
| Ambry Genetics | RCV000249385 | SCV000319978 | uncertain significance | Cardiovascular phenotype | 2021-01-13 | criteria provided, single submitter | clinical testing | The p.H244Y variant (also known as c.730C>T), located in coding exon 6 of the CASQ2 gene, results from a C to T substitution at nucleotide position 730. The histidine at codon 244 is replaced by tyrosine, an amino acid with some similar properties. This alteration has been reported in a proband with left ventricular non-compaction (LVNC) who also carried alterations in other cardiac-related genes (Hoedemaekers YM et al. Circ Cardiovasc Genet, 2010 Jun;3:232-9). This variant has also been reported in a sudden unexplained death cohort and a catecholaminergic polymorphic ventricular tachycardia (CPVT) cohort; however, clinical details were limited (Sanchez O et al. PLoS ONE, 2016 Dec;11:e0167358; Landstrom AP et al. Circ Arrhythm Electrophysiol, 2017 Apr;10:). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| ARUP Laboratories, |
RCV001001284 | SCV001158463 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 2 | 2023-10-16 | criteria provided, single submitter | clinical testing | The CASQ2 c.730_731delinsTG; p.His244Cys variant, to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 228471). This variant consists of two single nucleotide variants, c.730C>T (rs142036299) and c.731A>G (rs28730716), in adjacent nucleotides on the same chromosome. The individual variants, c.730C>T and c.731A>G, are found in the African population with overall allele frequencies of 0.23% (54/23932 alleles) and 8.3% (1990/23868 alleles), respectively, in the Genome Aggregation Database, and available data indicates that c.730C>T may always occur with c.731A>G. The histidine at codon 244 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the p.His244Cys variant is uncertain at this time. |