Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665858 | SCV000790047 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2017-03-14 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000665858 | SCV001163340 | likely pathogenic | Smith-Lemli-Opitz syndrome | criteria provided, single submitter | clinical testing | ||
| Gene |
RCV001568654 | SCV001792564 | pathogenic | not provided | 2020-01-28 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 15896653, 23293579, 20556518, 19390132, 22975760, 11427181, 10677299, 10995508, 12070263) |
| Invitae | RCV000665858 | SCV002228495 | pathogenic | Smith-Lemli-Opitz syndrome | 2023-07-25 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 109 of the DHCR7 protein (p.Leu109Pro). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 550951). This missense change has been observed in individuals with Smith–Lemli–Opitz syndrome (PMID: 10677299, 10995508, 11427181, 17441222). This variant is present in population databases (rs121912195, gnomAD 0.007%). |
| Ambry Genetics | RCV002442392 | SCV002612403 | likely pathogenic | Inborn genetic diseases | 2016-04-11 | criteria provided, single submitter | clinical testing | The p.L109P variant (also known as c.326T>C), located in coding exon 3 of the DHCR7 gene, results from a T to C substitution at nucleotide position 326. The leucine at codon 109 is replaced by proline, an amino acid with similar properties. This variant has been reported in multiple individuals with a diagnosis of Smith-Lemli-Opitz syndrome (SLOS) and second pathogenic mutation, (Witsch-Baumgartner M, Am. J. Hum. Genet. 2000 Feb; 66(2):402-12; Krakowiak PA, Am. J. Med. Genet. 2000 Sep; 94(3):214-27; Jira PE, Ann. Hum. Genet. 2001 May; 65(Pt 3):229-36; Jezela-Stanek A, J. Inherit. Metab. Dis. 2010 Dec; 33 Suppl 3:S241-8a); only one report confirmed this variant and the second pathogenic mutation to be in trans (Balogh I, Mol Syndromol 2012 Nov; 3(5):215-22). This variant was previously reported in the SNPDatabase as rs121912195. Based on data from the NHLBI Exome Sequencing Project (ESP), no alterations were observed among 12988 alleles tested (0.0%). Allele frequency data for this nucleotide position is not currently available from the 1000 Genomes Project. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. . |