Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Neuberg Centre For Genomic Medicine, |
RCV000024228 | SCV002073243 | pathogenic | Amelocerebrohypohidrotic syndrome | criteria provided, single submitter | clinical testing | The stop gained p.R157* in ROGDI (NM_024589.3) has been reported previously in affected in patients from Israel (Mory A et al, 2012). The variant has been submitted to ClinVar as Pathogenic based on the same publication. The nonsense mutation would truncate a highly conserved C-terminal domain and functional study suggest deleterious effecte (Morya A et al,2012). This variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. The p.R157* variant is a loss of function variant in the gene ROGDI gene. There are 5 downstream pathogenic loss of function variants, with the furthest variant being 82 residues downstream of the variant p.R157*. For these reasons, this variant has been classified as Pathogenic. | |
| Labcorp Genetics |
RCV000024228 | SCV002167326 | pathogenic | Amelocerebrohypohidrotic syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg157*) in the ROGDI gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ROGDI are known to be pathogenic (PMID: 22424600, 23086778). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Kohlschutter syndrome (PMID: 22482807, 24630287). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 31229). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000024228 | SCV002766463 | pathogenic | Amelocerebrohypohidrotic syndrome | 2022-11-10 | criteria provided, single submitter | clinical testing | Variant summary: ROGDI c.469C>T (p.Arg157X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 190756 control chromosomes. c.469C>T has been reported in the literature as a homozygous genotype in multiple consanguineous individuals from a Druze village in Northern Israel affected with Amelocerebrohypohidrotic Syndrome (also referred to as KohlschutterTonz Syndrome) (example, Mory_2012 subsequently cited by others). These data indicate that the variant is very likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV000024228 | SCV005646915 | pathogenic | Amelocerebrohypohidrotic syndrome | 2024-03-21 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000024228 | SCV000045519 | pathogenic | Amelocerebrohypohidrotic syndrome | 2012-04-06 | no assertion criteria provided | literature only |