Submissions for variant NM_001354604.2(MITF):c.1569G>A (p.Glu523=)

gnomAD frequency: 0.00003  dbSNP: rs200830148

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000286198	SCV000445940	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.
Illumina Laboratory Services, Illumina	RCV000343441	SCV000445941	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589785	SCV000696086	benign	not provided	2016-03-09	criteria provided, single submitter	clinical testing	Variant summary: This c.1248G>A variant affects a non-conserved nucleotide, resulting in synonymous amino acid change. 5/5 splice-site tools via Alamut predict that this variant does not affect normal splicing. This variant was found in 492/120528 control chromosomes from the broad and large populations of ExAC at a frequency of 0.004082, predominantly in South Asian population with an allele frequency of 0.02967 (488/16448 chromosomes) including 12 homozygous occurrences. These frequencies are significantly greater than the maximal expected frequency of a pathogenic allele (0.0000125) in this gene, suggesting this variant is a benign polymorphism mainly found in South Asian population. The variant has not been reported in individuals with phenotypes linked to this gene, to our knowledge. Taken together, this variant has been classified as Benign.
Invitae	RCV002520184	SCV001034667	benign	Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000589785	SCV001771613	likely benign	not provided	2020-12-09	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV001580039	SCV002550870	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316496	SCV004015855	likely benign	Melanoma, cutaneous malignant, susceptibility to, 8	2023-07-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001580039	SCV001809450	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001580039	SCV001921756	benign	not specified		no assertion criteria provided	clinical testing