Submissions for variant NM_181458.4(PAX3):c.246C>G (p.Cys82Trp)

dbSNP: rs777297575

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000660204	SCV000782204	likely pathogenic	Waardenburg syndrome type 3	2016-11-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000826182	SCV000967723	likely pathogenic	Rare genetic deafness	2018-07-31	criteria provided, single submitter	clinical testing	The p.Cys82Trp variant in PAX3 has been reported in ClinVar in a proband with Wa ardenburg syndrome and distal arthrogryposis (Variation ID: 547736, personal com munication). It is absent from large population databases including the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that the p.Cys82Trp variant m ay impact the protein. Also, the variant is located in a hotspot for pathogenic variants within the paired domain of the Pax-3 protein (Pingault 2010). In summa ry, the clinical significance of the p.Cys82Trp variant is likely pathogenic. AC MG/AMP Criteria applied: PM2, PP3, PP4, PS4_Supporting, PM1_Supporting.
CeGaT Center for Human Genetics Tuebingen	RCV002263924	SCV002544213	likely pathogenic	not provided	2022-04-01	criteria provided, single submitter	clinical testing