Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003618247 | SCV004390117 | pathogenic | Smith-Lemli-Opitz syndrome | 2023-03-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly303 amino acid residue in DHCR7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16044199, 20052364, 28503313). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. A different variant (c.907G>A) giving rise to the same protein effect has been determined to be pathogenic (PMID: 16044199, 20052364, 28503313). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 303 of the DHCR7 protein (p.Gly303Arg). |