Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000673491 | SCV000798699 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2018-03-21 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000673491 | SCV000893237 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2021-07-27 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000673491 | SCV002024079 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2021-01-13 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000673491 | SCV002244432 | pathogenic | Smith-Lemli-Opitz syndrome | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 443 of the DHCR7 protein (p.Arg443Cys). This variant is present in population databases (rs535561852, gnomAD 0.003%). This missense change has been observed in individuals with Smith-Lemli-Opitz syndrome (PMID: 20014133, 22211794). ClinVar contains an entry for this variant (Variation ID: 557359). 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.Arg443 amino acid residue in DHCR7. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000673491 | SCV002570704 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2022-07-20 | criteria provided, single submitter | clinical testing | Variant summary: DHCR7 c.1327C>T (p.Arg443Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 248964 control chromosomes. c.1327C>T has been reported in the literature in individuals affected with Smith-Lemli-Opitz Syndrome (example, Witsch-Baumgartner_2000, Tierney_2010, Kalb_2012, Sparks_2014, Rozdzynska-Swiakowska_2021, Wassif_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |