Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV003448533 | SCV004175977 | pathogenic | Developmental delay and seizures with or without movement abnormalities | 2023-11-28 | criteria provided, single submitter | clinical testing | Criteria applied: PS2,PS3,PS4_SUP,PM2_SUP,PP3 |
Labcorp Genetics |
RCV003525415 | SCV004267032 | pathogenic | Retinitis pigmentosa 59 | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 233 of the DHDDS protein (p.Pro233Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with DHDDS-related conditions (PMID: 34382076). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 2664983). 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 DHDDS protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects DHDDS function (PMID: 34382076). For these reasons, this variant has been classified as Pathogenic. |