Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001004587 | SCV001163685 | likely pathogenic | Smith-Lemli-Opitz syndrome | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001004587 | SCV001574191 | pathogenic | Smith-Lemli-Opitz syndrome | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 407 of the DHCR7 protein (p.Asn407Tyr). This variant is present in population databases (rs770819693, gnomAD 0.004%). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 10602371). 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: 813483). 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 with a positive predictive value of 95%. This variant disrupts the p.Asn407 amino acid residue in DHCR7. Other variant(s) that disrupt this residue have been observed in individuals with DHCR7-related conditions (PMID: 29455191), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Natera, |
RCV001004587 | SCV002093000 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2017-12-05 | no assertion criteria provided | clinical testing |