ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.622G>A (p.Glu208Lys)

gnomAD frequency: 0.00001  dbSNP: rs768503905
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001589923 SCV001824685 uncertain significance not provided 2023-01-20 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
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002291763 SCV002584699 uncertain significance Melanoma, cutaneous malignant, susceptibility to, 8 2022-10-05 criteria provided, single submitter clinical testing The MITF c.622G>A (p.Glu208Lys) missense change has a maximum population frequency of 0.0062% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with melanoma and renal cell carcinoma. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002501955 SCV002812172 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8; Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness 2021-07-20 criteria provided, single submitter clinical testing
Invitae RCV002592488 SCV003474449 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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 101 of the MITF protein (p.Glu101Lys). This variant is present in population databases (rs768503905, gnomAD 0.007%). 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: 1217664). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
GenomeConnect, ClinGen RCV001589923 SCV002074977 not provided not provided no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 10-29-2020 by Lab or GTR ID 507401. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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