ClinVar Miner

Submissions for variant NM_001360.3(DHCR7):c.1324C>G (p.His442Asp)

dbSNP: rs2135939533
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001376981 SCV001574197 likely pathogenic Smith-Lemli-Opitz syndrome 2020-09-13 criteria provided, single submitter clinical testing This sequence change replaces histidine with aspartic acid at codon 442 of the DHCR7 protein (p.His442Asp). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and aspartic acid. 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. This variant disrupts the p.His442 amino acid residue in DHCR7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28503313, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 not been reported in the literature in individuals with DHCR7-related conditions. This variant is not present in population databases (ExAC no frequency).

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