Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672461 | SCV000797567 | likely pathogenic | Lysosomal acid lipase deficiency | 2018-01-31 | criteria provided, single submitter | clinical testing | |
| Eurofins Ntd Llc |
RCV000731991 | SCV000859865 | pathogenic | not provided | 2018-02-26 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001861811 | SCV002234386 | pathogenic | Wolman disease | 2022-08-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 556450). This variant has not been reported in the literature in individuals affected with LIPA-related conditions. This variant is present in population databases (rs753796180, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Met117Ilefs*45) in the LIPA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LIPA are known to be pathogenic (PMID: 23485521). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001861811 | SCV003922576 | likely pathogenic | Wolman disease | 2023-03-18 | criteria provided, single submitter | clinical testing | Variant summary: LIPA c.350_351insCC (p.Met117IlefsX45) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.398del [p.Leu132_Ser133insTer], c.482del [p.Asn161fs]). The variant allele was found at a frequency of 8e-06 in 251452 control chromosomes (gnomAD). c.350_351insCC has been reported in the literature in at least one compound heterozygous individual affected with Lysosomal Acid Lipase Deficiency (Jones_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic, and two as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |