Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001384493 | SCV001584003 | pathogenic | Smith-Lemli-Opitz syndrome | 2020-05-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg443 amino acid residue in DHCR7. Other variant(s) that disrupt this residue have been observed in individuals with DHCR7-related conditions (PMID: 27513191), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with Smith-Lemli-Opitz syndrome (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs781687341, ExAC 0.01%). This sequence change replaces arginine with proline at codon 443 of the DHCR7 protein (p.Arg443Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. |