Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001390625 | SCV001592416 | pathogenic | Smith-Lemli-Opitz syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 432 of the DHCR7 protein (p.Tyr432Cys). This missense change has been observed in individual(s) with Smith–Lemli–Opitz syndrome (PMID: 15776424, 19390132, 23293579). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1076651). 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 DHCR7 protein function. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV001390625 | SCV002803643 | pathogenic | Smith-Lemli-Opitz syndrome | 2022-05-12 | criteria provided, single submitter | clinical testing |