Submissions for variant NM_000372.5(TYR):c.902C>G (p.Pro301Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004689518	SCV005185728	uncertain significance	not specified	2024-05-16	criteria provided, single submitter	clinical testing	Variant summary: TYR c.902C>G (p.Pro301Arg) results in a non-conservative amino acid change located in the Tyrosinase copper-binding domain (IPR002227) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251192 control chromosomes. c.902C>G has been reported in the literature in trans with pathogenic variants in at least 2 individuals affected with clinical features of Oculocutaneous Albinism (example, Wang_2020, Wei_2022). These data indicate that the variant may be associated with disease. 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: 32619251, 34838614, 37734845). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005006493	SCV005631359	likely pathogenic	Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2024-05-21	criteria provided, single submitter	clinical testing