Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002016221 | SCV002300500 | uncertain significance | not provided | 2024-12-06 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 2 of the CASQ1 gene. It does not directly change the encoded amino acid sequence of the CASQ1 protein. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with CASQ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1508598). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004690231 | SCV005184836 | likely benign | not specified | 2024-05-13 | criteria provided, single submitter | clinical testing | Variant summary: CASQ1 c.365-20_365-19delinsAA alters two nucleotides located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. Since this variant affects two neighboring nucleotides (c.365-20G>A and c.365-19C>A), the allele frequency of the complex could not be determined from population databases. However, the allele numbers, subpopulation frequencies, gender distribution and available age- and read data in carriers for the component variants suggests that these neighboring nucleotide changes are on the same haplotype in most carriers. Therefore, the complex variant allele is likely found at similar frequency to its component variants, i.e. ~3.2e-05 in 1419772 control chromosomes (i.e. ~45 carriers in the gnomAD database, v4.1 dataset). To our knowledge, no occurrence of c.365-20_365-19delinsAA in individuals affected with Myopathy Due To Calsequestrin And SERCA1 Protein Overload and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1508598). Based on the evidence outlined above, the variant was classified as likely benign. |