Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001102571 | SCV001259256 | uncertain significance | Primary hyperoxaluria type 3 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Clinical Biochemistry Laboratory, |
RCV001102571 | SCV004174278 | likely pathogenic | Primary hyperoxaluria type 3 | 2023-10-27 | criteria provided, single submitter | curation | ACMG:PM1 PM2 PM5 PP3 |
| Labcorp Genetics |
RCV003718319 | SCV004512774 | likely pathogenic | not provided | 2024-01-29 | 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 45 of the HOGA1 protein (p.Pro45Arg). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with HOGA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 877105). 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 HOGA1 protein function with a positive predictive value of 95%. This variant disrupts the p.Pro45 amino acid residue in HOGA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26342005; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |