Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV003225684 | SCV003921959 | likely pathogenic | Lysosomal acid lipase deficiency | 2020-07-22 | criteria provided, single submitter | clinical testing | 0102 - Loss of function is a known mechanism of disease in this gene and is associated with LAL-D. (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamine to proline. (I) 0252 - This variant is homozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting <i>in silico</i> predictions, but very high conservation. (I) 0601 - Variant is located in the well-established functional abhydrolase 1 domain, adjacent to the active site (p.Ser174) (PDB, UniProt, PMID: 31180157). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1101 - Very strong and specific phenotype match for this individual. (SP) 1206 - This variant has been shown to be paternally inherited (by trio analysis). Further inspection of the data suggests paternal isodisomy of chromosome 10. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |