Submissions for variant NM_181458.4(PAX3):c.784C>T (p.Arg262Ter)

dbSNP: rs886041319

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000315662	SCV000329710	pathogenic	not provided	2018-10-29	criteria provided, single submitter	clinical testing	The R262X variant in the PAX3 gene has been reported previously in multiple individuals with Waardenburg syndrome type 1 (Wildhardt et al., 2013; Jalilian et al., 2015). It has also been confirmed at GeneDx to have occurred de novo in an affected patient. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed in large population cohorts (Lek et al., 2016). We consider this variant to be pathogenic.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000660215	SCV000782215	pathogenic	Waardenburg syndrome type 1	2016-11-01	criteria provided, single submitter	clinical testing
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV000660215	SCV001478202	pathogenic	Waardenburg syndrome type 1	2019-01-01	criteria provided, single submitter	clinical testing
Invitae	RCV000315662	SCV004293982	pathogenic	not provided	2023-08-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280007). This premature translational stop signal has been observed in individual(s) with clinical features of Waardenburg syndrome (PMID: 23512835, 27759048). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg262*) in the PAX3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAX3 are known to be pathogenic (PMID: 20127975, 23512835).