Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV000512759 | SCV002768167 | pathogenic | Galloway-Mowat syndrome 3 | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Galloway-Mowat syndrome 3 (GAMOS; MIM#617729). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (31 heterozygotes, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated tRNA N6-adenosine threonylcarbamoyltransferase domain (DECIPHER). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been identified in multiple individuals with GAMOS and has been proposed as a Taiwanese/Chinese founder allele (PMIDs: 28805828, 31564459, 33333793). (SP) 0902 - This variant has moderate evidence for segregation with disease. This variant has been shown to segregate in affected siblings across two families (PMIDs: 28805828, 31564459). (SP) 1002 - This variant has moderate functional evidence supporting abnormal protein function. The p.(Arg247Gln) mutant construct failed to rescue the proliferation rate of OSGEP knockdown human podacyte cells and was only able to partially rescue growth defects in yeast lacking the yeast ortholog of OSGEP ( kae1 ), compared to WT (PMID: 28805828). (SP) 1205 - This variant has been shown to be maternally inherited (LABID). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Invitae | RCV002524976 | SCV003442776 | pathogenic | not provided | 2023-07-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 247 of the OSGEP protein (p.Arg247Gln). This variant is present in population databases (rs773173317, gnomAD 0.1%). This missense change has been observed in individuals with Galloway-Mowat syndrome (PMID: 28805828, 31564459). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 444893). 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 OSGEP protein function. Experimental studies have shown that this missense change affects OSGEP function (PMID: 28805828). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000512759 | SCV000609476 | pathogenic | Galloway-Mowat syndrome 3 | 2017-10-30 | no assertion criteria provided | literature only | |
| Yale Center for Mendelian Genomics, |
RCV001849393 | SCV002106591 | uncertain significance | Nephrotic syndrome | 2017-11-10 | no assertion criteria provided | literature only |