Submissions for variant NM_181458.4(PAX3):c.667C>T (p.Arg223Ter)

dbSNP: rs772241382

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000599259	SCV000709897	pathogenic	not provided	2024-05-21	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20478267, 9654197, 17254487, 25525159, 8019556, 20664692, 9541113, 26275939, 30978479, 34008892, 34142234, 34599368, 37211999, 35982127, 27759048, 8533800)
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000599259	SCV001467991	pathogenic	not provided	2020-08-04	criteria provided, single submitter	clinical testing
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV001290145	SCV001478198	pathogenic	Waardenburg syndrome type 1	2019-01-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001335583	SCV001528762	pathogenic	Waardenburg syndrome type 3	2018-04-23	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as pathogenic [PMID 8019556, 26275939, 27759048, 25525159]
Otorhinolaryngology Lab - LIM32, University of Sao Paulo School of Medicine Clinics Hospital	RCV001290145	SCV001792239	pathogenic	Waardenburg syndrome type 1		criteria provided, single submitter	research	Familial case: proband with bilateral profound sensorineural hearing loss, Telecanthus, nasal wings hypoplasia and hyperplasia of nasal root, and synophris, Blue hypoplastic irides and white hair forelock. Paternal grandmother and paternal aunt are also carriers of this variant and affected by only facial dysmorphisms
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV001290145	SCV001976945	pathogenic	Waardenburg syndrome type 1	2021-10-01	criteria provided, single submitter	clinical testing	PVS1, PM1, PM2, PP3, PP4, PP5
Labcorp Genetics (formerly Invitae), Labcorp	RCV000599259	SCV002240644	pathogenic	not provided	2025-02-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg223*) 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). This variant is present in population databases (rs772241382, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Waardenburg syndrome (PMID: 8019556, 30978479). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 503680). For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV001290145	SCV004171872	pathogenic	Waardenburg syndrome type 1		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000599259	SCV004811470	pathogenic	not provided	2024-03-01	criteria provided, single submitter	clinical testing	PAX3: PVS1, PM2, PS4:Moderate