Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002041867 | SCV002113764 | pathogenic | Wolman disease | 2021-03-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 342 of the LIPA protein (p.Gly342Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). A different variant (c.1024G>A) giving rise to the same protein effect has been determined to be pathogenic (PMID: 10562460, 28881270, 24048164, 23485521). This suggests that this variant is also likely to be causative of disease. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LIPA protein function. For these reasons, this variant has been classified as Pathogenic. |