Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000372931 | SCV000329634 | pathogenic | not provided | 2023-06-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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: 10868211, 8845842, 21867959, 9279758, 9654197, 20478267, 15726414, 30973918, 32747562, 34142234, Lee2022[paper], 8589691, 36331148, 31427586) |
Center for Human Genetics, |
RCV000660219 | SCV000782219 | pathogenic | Waardenburg syndrome type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Genetic Testing Center for Deafness, |
RCV000660219 | SCV001478204 | pathogenic | Waardenburg syndrome type 1 | 2019-01-01 | criteria provided, single submitter | clinical testing | |
King Laboratory, |
RCV000660219 | SCV001976369 | pathogenic | Waardenburg syndrome type 1 | 2020-08-01 | criteria provided, single submitter | research | PAX3 c.812G>A, p.R271H alters a residue of PAX3 conserved throughout all sequenced vertebreates and has been reported multiple times as a pathogenic variant. It is heterozygous in a Palestinian child with features of Waardenburg syndrome (Abu Rayyan 2020). |
Invitae | RCV000372931 | SCV002223887 | pathogenic | not provided | 2023-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg271 amino acid residue in PAX3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8589691, 8799378, 9654197, 20199465). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PAX3 protein function. ClinVar contains an entry for this variant (Variation ID: 279964). This missense change has been observed in individuals with Waardenburg syndrome (PMID: 8589691, 9654197, 20478267). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 271 of the PAX3 protein (p.Arg271His). |
Fulgent Genetics, |
RCV002500967 | SCV002813970 | pathogenic | Alveolar rhabdomyosarcoma; Waardenburg syndrome type 1; Craniofacial-deafness-hand syndrome; Waardenburg syndrome type 3 | 2022-04-19 | criteria provided, single submitter | clinical testing |