Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000660218 | SCV000782218 | pathogenic | Waardenburg syndrome type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Genetic Testing Center for Deafness, |
RCV000660218 | SCV001478203 | pathogenic | Waardenburg syndrome type 1 | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000660218 | SCV001520004 | pathogenic | Waardenburg syndrome type 1 | 2019-12-06 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Invitae | RCV001861717 | SCV002241278 | pathogenic | not provided | 2021-07-17 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Arg271 amino acid residue in PAX3. Other variant(s) that disrupt this residue have been observed in individuals with PAX3-related conditions (PMID: 9654197, 8589691), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with autosomal dominate Waardenburg syndrome (PMID: 8589691, 8799378, 9654197, 20199465). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 547748). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 271 of the PAX3 protein (p.Arg271Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. |