Submissions for variant NM_001354604.2(MITF):c.1031+1G>A

dbSNP: rs1559749017

Total submissions: 5

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	RCV000721950	SCV001478208	pathogenic	Waardenburg syndrome type 2A	2019-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001557795	SCV001779623	pathogenic	not provided	2023-09-25	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 20127975, 32013026, 30394532, 31541171, 34142234)
Invitae	RCV003767887	SCV004569775	pathogenic	Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8	2022-11-18	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 545015). This variant is also known as c.1013+1G>A. Disruption of this splice site has been observed in individual(s) with deafness and/or Waardenburg syndrome (PMID: 20127975, 30394532, 31541171, 32013026, 34142234). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 7 of the MITF gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MITF are known to be pathogenic (PMID: 8659547, 20127975).
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000721950	SCV000763284	pathogenic	Waardenburg syndrome type 2A	2018-05-15	no assertion criteria provided	research
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV000770828	SCV000902329	likely pathogenic	Waardenburg syndrome type 1	2019-02-26	no assertion criteria provided	case-control