Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001367082 | SCV001563417 | uncertain significance | Wolman disease | 2022-07-17 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 395 of the LIPA protein (p.Met395Ile). This variant is not present in population databases (gnomAD no frequency). 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: 1057996). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002341787 | SCV002637806 | uncertain significance | Cardiovascular phenotype | 2023-08-22 | criteria provided, single submitter | clinical testing | The c.1185G>A (p.M395I) alteration is located in exon 10 (coding exon 9) of the LIPA gene. This alteration results from a G to A substitution at nucleotide position 1185, causing the methionine (M) at amino acid position 395 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV001826057 | SCV002088903 | uncertain significance | Lysosomal acid lipase deficiency | 2020-02-28 | no assertion criteria provided | clinical testing |