Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001377630 | SCV001575013 | pathogenic | Renal coloboma syndrome; Focal segmental glomerulosclerosis 7 | 2022-02-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg140 amino acid residue in PAX2. Other variant(s) that disrupt this residue have been observed in individuals with PAX2-related conditions (PMID: 30241513, 32203253), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 1066591). This missense change has been observed in individual(s) with PAX2-related conditions (PMID: 29973660, 30076350, 31060108, 31576025, 31692565). In at least one individual the variant was observed to be de novo. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 140 of the PAX2 protein (p.Arg140Trp). |
| Fulgent Genetics, |
RCV001377630 | SCV002787193 | pathogenic | Renal coloboma syndrome; Focal segmental glomerulosclerosis 7 | 2024-02-16 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004531187 | SCV004720765 | pathogenic | PAX2-related disorder | 2023-11-21 | no assertion criteria provided | clinical testing | The PAX2 c.418C>T variant is predicted to result in the amino acid substitution p.Arg140Trp. This variant has not been reported in a large population database, indicating this variant is rare. The p.Arg140 residue is highly conserved during evolution. This variant has been reported to be pathogenic for PAX2-related disorders (see for example, Chen et al. 2021. PubMed ID: 34031707, Supplementary Table 2 ; Rossanti et al. 2020. PubMed ID: 32203253; Sun et al. 2018. PubMed ID: 30076350, Supplementary Table 1). Other substitutions at the same codon have also been reported to be pathogenic for PAX2-related disorders (Human Gene Mutation Database). This variant is interpreted as pathogenic. |