Submissions for variant NM_001354604.2(MITF):c.880+9C>G

gnomAD frequency: 0.00203  dbSNP: rs181810413

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000221103	SCV000269243	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	880+9C>G in intron 6 of MITF: This variant is not expected to have clinical sign ificance because it is not located within the conserved splice consensus sequenc e. It has been identified in 0.3% (30/8600) of European American chromosomes fro m a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washin gton.edu/EVS; dbSNP rs181810413).
PreventionGenetics, part of Exact Sciences	RCV000221103	SCV000303138	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000340493	SCV000445924	benign	Waardenburg syndrome type 2A	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000405831	SCV000445925	benign	Tietz syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588948	SCV000696088	benign	not provided	2016-03-04	criteria provided, single submitter	clinical testing	Variant summary: c.559+9C>G affects a non-conserved nucleotide, resulting in an intronic change. Mutation taster predicts this variant to be a polymorphism. 4/5 in-silico tool predicts no significant changes on RNA splicing. ESEfinder predicts gain of binding motifs for RNA slicing enhancers. This variant was found in 196/120978 control chromosomes at a frequency of 0.0016201, which is more than 129 times of maximal expected frequency of a pathogenic allele (0.0000125), suggesting this variant is benign. . This variant has not been, to our knowledge, reported in affected individuals via publications/ clinical laboratories, or databases; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant was classified as Benign.
GeneDx	RCV000221103	SCV000731001	likely benign	not specified	2017-08-29	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088700	SCV001001134	benign	Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8	2025-02-03	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000221103	SCV001476553	benign	not specified	2019-10-24	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002257517	SCV002536416	likely benign	Hereditary cancer-predisposing syndrome	2020-12-22	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000221103	SCV002550862	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316183	SCV004015854	benign	Melanoma, cutaneous malignant, susceptibility to, 8	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000588948	SCV005264092	likely benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000588948	SCV001809245	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000221103	SCV001917823	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000588948	SCV001952355	likely benign	not provided		no assertion criteria provided	clinical testing