Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519248 | SCV000620358 | pathogenic | not provided | 2020-06-24 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016) 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: 29100083, 31780880) |
| Institute of Medical Genetics and Applied Genomics, |
RCV000519248 | SCV001480068 | likely pathogenic | not provided | 2021-02-01 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV000578122 | SCV001934465 | uncertain significance | Developmental delay and seizures with or without movement abnormalities | 2021-03-03 | criteria provided, single submitter | clinical testing | Despite strong evidence for its pathogenicity, this variant has to be classified as of unknown significance, according to the ACMG-criteria (Richards et al., 2015) |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV000578122 | SCV002061811 | pathogenic | Developmental delay and seizures with or without movement abnormalities | 2021-12-22 | criteria provided, single submitter | clinical testing | PS2, PS4, PP3, PM2 |
| Invitae | RCV001858011 | SCV002216078 | pathogenic | Retinitis pigmentosa 59 | 2022-09-07 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 451635). This missense change has been observed in individual(s) with autosomal dominant developmental and epileptic encephalopathy (PMID: 29100083, 31780880). In at least one individual the variant was observed to be de novo. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 37 of the DHDDS protein (p.Arg37His). |
| 3billion | RCV000578122 | SCV002572747 | pathogenic | Developmental delay and seizures with or without movement abnormalities | 2022-09-01 | criteria provided, single submitter | clinical testing | This missense variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.76; 3Cnet: 0.49). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000451635). The variant has been previously reported as de novo in a similarly affected individual (PMID: 29100083 , 29100083). A different missense change at the same codon (p.Arg37Cys) has been reported to be associated with DHDDS-related disorder (ClinVar ID: VCV001214981). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
| Laboratory of Medical Genetics, |
RCV000578122 | SCV002760060 | pathogenic | Developmental delay and seizures with or without movement abnormalities | 2022-11-29 | criteria provided, single submitter | research | |
| OMIM | RCV000578122 | SCV000679984 | pathogenic | Developmental delay and seizures with or without movement abnormalities | 2018-01-24 | no assertion criteria provided | literature only |