Submissions for variant NM_000372.5(TYR):c.346C>T (p.Arg116Ter)

gnomAD frequency: 0.00003  dbSNP: rs61753256

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000503968	SCV000597784	pathogenic	Tyrosinase-negative oculocutaneous albinism	2017-03-20	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763289	SCV000893936	pathogenic	Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; Ocular albinism with congenital sensorineural hearing loss; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000085948	SCV001768243	pathogenic	not provided	2023-02-03	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: 31077556, 23324268, 10671066, 26252096, 28507374, 31199599, 34426522, 32552135, 35923705, 28378818, 30996339)
Genome-Nilou Lab	RCV000503968	SCV001821927	pathogenic	Tyrosinase-negative oculocutaneous albinism	2021-07-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085948	SCV002239440	pathogenic	not provided	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg116*) 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 (rs61753256, gnomAD 0.03%). This premature translational stop signal has been observed in individuals with oculocutaneous albinism (PMID: 31077556, 31199599). ClinVar contains an entry for this variant (Variation ID: 99565). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003467007	SCV004207620	pathogenic	SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2023-12-14	criteria provided, single submitter	clinical testing
Medical Molecular Genetics Department, National Research Center	RCV000503968	SCV005091107	pathogenic	Tyrosinase-negative oculocutaneous albinism		criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796014	SCV005415690	pathogenic	Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PM3_Strong+PP4
Fulgent Genetics, Fulgent Genetics	RCV005003463	SCV005631915	pathogenic	Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2024-02-09	criteria provided, single submitter	clinical testing
Retina International	RCV000085948	SCV000118091	not provided	not provided		no assertion provided	not provided
PreventionGenetics, part of Exact Sciences	RCV004739350	SCV005361014	pathogenic	TYR-related disorder	2024-08-01	no assertion criteria provided	clinical testing	The TYR c.346C>T variant is predicted to result in premature protein termination (p.Arg116*). This variant has been reported in multiple individuals with oculocutaneous albinism (see for examples: Oetting et al. 1998. PubMed ID: 10671066; Wei et al. 2013. PubMed ID: 23324268; Lin et al. 2019. PubMed ID: 31199599). This variant is reported in 0.025% of alleles in individuals of East Asian descent in gnomAD. Nonsense variants in TYR are an established mechanism of disease. Given the evidence, we interpret this variant as pathogenic.