Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000079646 | SCV000230166 | pathogenic | not provided | 2013-03-18 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000079646 | SCV000491237 | pathogenic | not provided | 2020-10-26 | criteria provided, single submitter | clinical testing | Not observed 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: 11175299, 21724437, 9653161, 12914579, 17497248, 24500076, 10677299, 23042628, 15521979, 21990131, 18249054, 10814720, 16983147) |
Counsyl | RCV000178160 | SCV000792783 | pathogenic | Smith-Lemli-Opitz syndrome | 2017-07-13 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000178160 | SCV000959206 | pathogenic | Smith-Lemli-Opitz syndrome | 2023-07-16 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 51 of the DHCR7 protein (p.Pro51Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Smith- Lemli-Opitz syndrome (PMID: 9653161, 16181459). 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: 93712). 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. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000178160 | SCV002600746 | pathogenic | Smith-Lemli-Opitz syndrome | 2022-10-27 | criteria provided, single submitter | clinical testing | Variant summary: DHCR7 c.151C>T (p.Pro51Ser) 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 was absent in 241350 control chromosomes (gnomAD). c.151C>T has been reported in the literature in multiple individuals affected with Smith-Lemli-Opitz Syndrome (examples: Fitzky_1998, Ciara_2004 and Bianconi_2011). These data indicate that the variant is very likely to be associated with disease. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Natera, |
RCV000178160 | SCV002093075 | pathogenic | Smith-Lemli-Opitz syndrome | 2017-11-28 | no assertion criteria provided | clinical testing |