Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Human Genetics, |
RCV000626392 | SCV000678727 | likely pathogenic | Waardenburg syndrome type 1 | 2017-03-01 | criteria provided, single submitter | research | |
Center for Human Genetics, |
RCV000626392 | SCV000782197 | likely pathogenic | Waardenburg syndrome type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Equipe Genetique des Anomalies du Developpement, |
RCV001526650 | SCV001737081 | likely pathogenic | Intellectual disability | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001859999 | SCV002258488 | likely pathogenic | not provided | 2023-09-19 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects PAX3 function (PMID: 18325909, 28381738). 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 PAX3 protein function. ClinVar contains an entry for this variant (Variation ID: 488034). This missense change has been observed in individuals with autosomal dominant Waardenburg syndrome (PMID: 28686331, 29407415). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 42 of the PAX3 protein (p.Gly42Arg). |
Gene |
RCV001859999 | SCV002520118 | likely pathogenic | not provided | 2022-05-13 | criteria provided, single submitter | clinical testing | Not observed 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: 28381738, 34038854, 18325909, 16280008, 8406487, 29407415, 7867071, 28686331) |