Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169290 | SCV000220606 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2014-08-20 | criteria provided, single submitter | literature only | |
Invitae | RCV000169290 | SCV000630076 | pathogenic | Smith-Lemli-Opitz syndrome | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 154 of the DHCR7 protein (p.Thr154Met). This variant is present in population databases (rs143312232, gnomAD 0.0009%). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 10677299, 10995508, 11427181, 15896653, 18249054, 22391996). ClinVar contains an entry for this variant (Variation ID: 188923). 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%. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000169290 | SCV001163335 | pathogenic | Smith-Lemli-Opitz syndrome | criteria provided, single submitter | clinical testing | ||
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169290 | SCV001362509 | pathogenic | Smith-Lemli-Opitz syndrome | 2020-09-03 | criteria provided, single submitter | clinical testing | Variant summary: DHCR7 c.461C>T (p.Thr154Met) 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 249850 control chromosomes (gnomAD). c.461C>T has been reported in the literature in multiple individuals affected with Smith-Lemli-Opitz Syndrome (Wassif_2005, Jira_2001, Krakowiak_2000, Witsch-Baumgartner_2000, Eroglu_2017). These data indicate that the variant is very likely to be associated with disease. Experimental evidence evaluating an impact on protein function demonstrated patients carrying the variant of interest along with other pathogenic variants to exhibit decreased fractional cholesterol synthesis and expression studies showed this variant results in reduced protein expression in cell line (Witsch-Baumgartner_DHCR7_AJHG_2000, Wassif_2005). One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Fulgent Genetics, |
RCV000169290 | SCV002809842 | pathogenic | Smith-Lemli-Opitz syndrome | 2021-10-13 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000169290 | SCV004234310 | pathogenic | Smith-Lemli-Opitz syndrome | 2023-03-27 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000169290 | SCV002093049 | pathogenic | Smith-Lemli-Opitz syndrome | 2017-11-28 | no assertion criteria provided | clinical testing |