ClinVar Miner

Submissions for variant NM_205861.3(DHDDS):c.308G>A (p.Arg103His)

gnomAD frequency: 0.00003  dbSNP: rs115712846
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001341105 SCV001534953 uncertain significance Retinitis pigmentosa 59 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 103 of the DHDDS protein (p.Arg103His). This variant is present in population databases (rs115712846, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with DHDDS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1037882). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DHDDS protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center RCV004783959 SCV005397626 uncertain significance Developmental delay and seizures with or without movement abnormalities 2024-06-25 criteria provided, single submitter clinical testing This sequence variant is a single nucleotide substitution (G>A) at position 308 of the coding sequence of the DHDDS gene that results in an arginine to histidine amino acid change at residue 103 of the dehydrodolichyl diphosphate synthase subunit protein. The 103 residue falls in the cis-PTase catalytic domain (UniProt). This is a previously reported variant (ClinVar 1037882) that has not been observed in an individual affected by a DHDDS-related disorder in the published literature, to our knowledge. This variant is present in 55 of 1614050 alleles (0.0034%) in the gnomAD v4.1.0 population dataset. Multiple bioinformatic tools predict that this amino acid change would be damaging, and the Arg103 residue at this position is highly conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: PM2, PP3
Natera, Inc. RCV001341105 SCV002085954 uncertain significance Retinitis pigmentosa 59 2021-09-13 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.