Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779348 | SCV000915943 | uncertain significance | Combined deficiency of sialidase AND beta galactosidase | 2017-10-24 | criteria provided, single submitter | clinical testing | The CTSA c.822C>A (p.Cys274Ter) variant is a stop-gained variant.A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for galactosialidosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV000779348 | SCV002235007 | pathogenic | Combined deficiency of sialidase AND beta galactosidase | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys274*) in the CTSA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTSA are known to be pathogenic (PMID: 15110321, 23915561). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CTSA-related conditions. ClinVar contains an entry for this variant (Variation ID: 632374). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |