Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001378034 | SCV001575517 | likely pathogenic | Smith-Lemli-Opitz syndrome | 2020-08-26 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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. This variant has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 23293579). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 125 of the DHCR7 protein (p.Tyr125Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. |