Submissions for variant NM_001354604.2(MITF):c.1096C>T (p.Arg366Ter)

dbSNP: rs2066482593

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV001290156	SCV001478213	pathogenic	Waardenburg syndrome type 2A	2019-01-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002543007	SCV003525337	pathogenic	Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8	2023-08-03	criteria provided, single submitter	clinical testing	Experimental studies have shown that this premature translational stop signal affects MITF function (PMID: 8659547, 23787126). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This sequence change creates a premature translational stop signal (p.Arg259*) in the MITF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MITF are known to be pathogenic (PMID: 8659547, 20127975). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal dominant Waardenburg syndrome (PMID: 8659547, 27759048, 31213145). This variant is also known as C(895)>T (259R>Stop). ClinVar contains an entry for this variant (Variation ID: 995922).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001729834	SCV001977771	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001729834	SCV001979670	pathogenic	not provided		no assertion criteria provided	clinical testing