Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001033481 | SCV001196788 | likely pathogenic | Lysosomal acid lipase deficiency | 2019-10-30 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 9-10 of the LIPA gene. The 5' boundary is likely confined to intron 8. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has not been reported in the literature in individuals with LIPA-related conditions. This variant disrupts the p.Gly342 amino acid residue in LIPA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10562460, 24048164, 28881270, 22227072, 29196158). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Invitae | RCV003117709 | SCV003788824 | likely pathogenic | Wolman disease | 2022-06-17 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 9-10 of the LIPA gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. A similar copy number variant has been observed in individual(s) with clinical features of LIPA-related conditions (Invitae). This variant disrupts the p.Gly342 amino acid residue in LIPA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10562460, 22227072, 24048164, 28881270, 29196158). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |