Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001942267 | SCV002232072 | pathogenic | Smith-Lemli-Opitz syndrome | 2022-11-25 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1455236). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asn407 amino acid residue in DHCR7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10602371, 12818773, 29455191). 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. This missense change has been observed in individual(s) with Smith–Lemli–Opitz syndrome (PMID: 2945519). This variant is present in population databases (rs746591926, gnomAD 0.002%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 407 of the DHCR7 protein (p.Asn407Ser). |