Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002015208 | SCV002283295 | uncertain significance | Wolman disease | 2022-06-05 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 378 of the LIPA protein (p.Ile378Thr). This variant is present in population databases (rs778013279, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with LIPA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1495192). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV002443018 | SCV002612275 | uncertain significance | Cardiovascular phenotype | 2021-07-12 | criteria provided, single submitter | clinical testing | The p.I378T variant (also known as c.1133T>C), located in coding exon 9 of the LIPA gene, results from a T to C substitution at nucleotide position 1133. The isoleucine at codon 378 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Department of Traditional Chinese Medicine, |
RCV003329429 | SCV004036020 | uncertain significance | Lysosomal acid lipase deficiency | no assertion criteria provided | clinical testing | We identified a patient clinically diagnosed with lysosomal acid lipase deficiency who carried a heterozygous mutation in LIPA. Lysosomal acid lipase deficiency was originally recessive, but a patient with a heterozygous mutation in LIPA was found to fulfill the clinical diagnosis in our study. The mutation is consistent with "PM1（Located in a mutational hot spot and/or critical and well-established functional domain without benign variation.）+PM2(Absent from controls in Exome Sequencing Project, 1000 Genomes or ExAC.)" according to the scores in the ACMG, and the possibility that this variant causes the disease cannot be excluded; therefore, its association with the disease requires further investigation. A literature search of genes, cDNA changes, and amino acid changes did not identify any publications based on this search. Therefore, the variant was categorized as a variant of unknown significance for the disease. |