Submissions for variant NM_001354604.2(MITF):c.1084C>T (p.Arg362Ter)

dbSNP: rs1057517966

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413197	SCV000491214	pathogenic	not provided	2022-05-31	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect on trans-activation of the TYR promoter, leading to haploinsufficiency (Wang et al., 2018); 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 in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20478267, 24194866, 22320238, 26512583, 28777840, 29407415, 29094203, 29531335, 33045145, 27759048, 30394532, 30936914, 33597575)
Laboratory of Human Genetics, Universidade de São Paulo	RCV000626399	SCV000678734	likely pathogenic	Waardenburg syndrome type 2A	2017-03-01	criteria provided, single submitter	research
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000626399	SCV000781749	likely pathogenic	Waardenburg syndrome type 2A	2016-11-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000413197	SCV001248804	pathogenic	not provided	2019-12-01	criteria provided, single submitter	clinical testing
Invitae	RCV003766148	SCV004569529	pathogenic	Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8	2023-10-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg255*) 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 Waardenburg syndrome (PMID: 20478267, 22320238, 24194866, 29531335, 30394532). ClinVar contains an entry for this variant (Variation ID: 372755). For these reasons, this variant has been classified as Pathogenic.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000721949	SCV000763445	pathogenic	Congenital sensorineural hearing impairment	2018-05-15	no assertion criteria provided	research