Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000274996 | SCV000329332 | pathogenic | not provided | 2016-09-22 | criteria provided, single submitter | clinical testing | The H119L missense pathogenic variant has been reported previously in association with SLOS (Witsch-Baumgartner et al., 2001). |
| Labcorp Genetics |
RCV000007182 | SCV002247477 | pathogenic | Smith-Lemli-Opitz syndrome | 2022-09-02 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs28938174, gnomAD 0.0009%). This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 119 of the DHCR7 protein (p.His119Leu). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 9683613). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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: 6780). |
| Fulgent Genetics, |
RCV000007182 | SCV002802353 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2022-01-11 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004585991 | SCV005077629 | uncertain significance | not specified | 2024-04-17 | criteria provided, single submitter | clinical testing | Variant summary: DHCR7 c.356A>T (p.His119Leu) 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 4e-06 in 250946 control chromosomes (gnomAD). c.356A>T has been reported in the literature in individuals affected with Smith-Lemli-Opitz Syndrome (Waterham_1998, Witsch-Baumgartner_2001). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 9683613, 11175299). ClinVar contains an entry for this variant (Variation ID: 6780). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| OMIM | RCV000007182 | SCV000027378 | pathogenic | Smith-Lemli-Opitz syndrome | 1998-08-01 | no assertion criteria provided | literature only |