ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.1229C>T (p.Thr410Met)

gnomAD frequency: 0.00005  dbSNP: rs369552358
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001571201 SCV001795625 uncertain significance not provided 2023-12-18 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001571201 SCV002009383 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002495910 SCV002793597 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8; Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness 2021-11-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002570780 SCV003282528 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 303 of the MITF protein (p.Thr303Met). This variant is present in population databases (rs369552358, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MITF-related conditions. ClinVar contains an entry for this variant (Variation ID: 1204757). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MITF protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004039370 SCV004906404 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-16 criteria provided, single submitter clinical testing The c.908C>T (p.T303M) alteration is located in exon 9 (coding exon 9) of the MITF gene. This alteration results from a C to T substitution at nucleotide position 908, causing the threonine (T) at amino acid position 303 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.