Submissions for variant NM_000372.5(TYR):c.1204C>T (p.Arg402Ter)

gnomAD frequency: 0.00004  dbSNP: rs62645917

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194121	SCV000249333	pathogenic	Tyrosinase-negative oculocutaneous albinism	2015-07-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000085909	SCV000329960	pathogenic	not provided	2023-05-07	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 18326704, 8128955, 18463683, 29036293, 29437493, 29427439, 28976636, 34426522, 31589614, 28667292, 28266639, 35894802, 34838614, 33124154, 31077556)
Eurofins Ntd Llc (ga)	RCV000085909	SCV000857011	pathogenic	not provided	2017-09-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000085909	SCV001248575	pathogenic	not provided	2023-07-01	criteria provided, single submitter	clinical testing	TYR: PVS1, PM3:Strong, PM2, PP4:Moderate
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814059	SCV001755182	pathogenic	Abnormality of the skin	2021-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000194121	SCV001821967	pathogenic	Tyrosinase-negative oculocutaneous albinism	2021-07-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085909	SCV002227770	pathogenic	not provided	2025-02-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg402*) in the TYR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TYR are known to be pathogenic (PMID: 23504663). This variant is present in population databases (rs62645917, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 29345414). ClinVar contains an entry for this variant (Variation ID: 99542). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003460777	SCV004207554	pathogenic	SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2024-03-29	criteria provided, single submitter	clinical testing
NHS Central & South Genomic Laboratory Hub	RCV004782234	SCV005393978	pathogenic	Albinism or congenital nystagmus	2024-11-11	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005008003	SCV005631385	pathogenic	Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2023-12-29	criteria provided, single submitter	clinical testing
Retina International	RCV000085909	SCV000118052	not provided	not provided		no assertion provided	not provided
University of Washington Center for Mendelian Genomics, University of Washington	RCV000755079	SCV000882897	likely pathogenic	Nonsyndromic Oculocutaneous Albinism	2017-03-07	no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV004739348	SCV005351481	pathogenic	TYR-related disorder	2024-08-01	no assertion criteria provided	clinical testing	The TYR c.1204C>T variant is predicted to result in premature protein termination (p.Arg402*). This variant has been reported many times in individuals with oculocutaneous albinism (see for examples: Gershoni-Baruch et al. 1994. PubMed ID: 8128955; Shahzad et al. 2017. PubMed ID: 28266639; Marti et al. 2017. PubMed ID: 28976636; Table S1, Wei et al. 2022. PubMed ID: 34838614). This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD. Nonsense variants in TYR are an established mechanism of disease. Given the evidence, we interpret this variant as pathogenic.