Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001889812 | SCV002138993 | pathogenic | Hereditary spastic paraplegia 39 | 2023-03-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1377033). 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 PNPLA6 protein function. For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individual(s) with PNPLA6-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1061 of the PNPLA6 protein (p.Tyr1061Cys). This variant is not present in population databases (gnomAD no frequency). |