ClinVar

Description

Variant summary: TYR c.646T>A (p.Leu216Met) results in a conservative amino acid change located in the Tyrosinase copper-binding domain (IPR002227) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 250976 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.646T>A has been reported at a compound heterozygous state along with a second pathogenic variant in one individual affected with Oculocutaneous Albinism (Oetting_1993). In another case with inherited eye diseases, this variant was seen along with two other pathogenic missense variants in TYR (Schlottmann_2023). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31589614, 8434585, 37217489). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.