Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000412788 | SCV000490514 | pathogenic | not provided | 2022-02-22 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29300326, 11111101, 12914579, 16392899, 24500076, 11298379, 9714007, 10995508, 11186897, 11471166, 23603282, 12070263) |
| Athena Diagnostics | RCV000412788 | SCV001143731 | likely pathogenic | not provided | 2020-09-21 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant appears to segregate with disease in at least one family, however, the available information does not rule out segregation due to chance. Assessment of experimental evidence suggests this variant results in abnormal protein function. Elevated levels of 7-DHC were present in patients (PMID: 9714007). |
| Baylor Genetics | RCV000007191 | SCV001163698 | pathogenic | Smith-Lemli-Opitz syndrome | criteria provided, single submitter | clinical testing | ||
| Invitae | RCV000007191 | SCV001203505 | pathogenic | Smith-Lemli-Opitz syndrome | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 289 of the DHCR7 protein (p.Thr289Ile). This variant is present in population databases (rs121909765, gnomAD 0.004%). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 10995508, 11298379). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6789). 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. |
| Ambry Genetics | RCV002371766 | SCV002684438 | pathogenic | Inborn genetic diseases | 2019-05-22 | criteria provided, single submitter | clinical testing | The p.T289I pathogenic mutation (also known as c.866C>T), located in coding exon 6 of the DHCR7 gene, results from a C to T substitution at nucleotide position 866. The threonine at codon 289 is replaced by isoleucine, an amino acid with similar properties. This mutation has been reported in multiple individuals with Smith-Lemli-Opitz syndrome, in conjunction with a second disease-causing allele (Krakowiak PA et al. Am. J. Med. Genet., 2000 Sep;94:214-27; Nowaczyk MJ et al. Am. J. Med. Genet., 2001 Apr;100:162-3). Based on data from gnomAD, the T allele has an overall frequency of approximately 0.0016% (4/251110). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| OMIM | RCV000007191 | SCV000027387 | pathogenic | Smith-Lemli-Opitz syndrome | 2001-04-22 | no assertion criteria provided | literature only | |
| Counsyl | RCV000007191 | SCV000486161 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2016-04-06 | no assertion criteria provided | clinical testing |