Submissions for variant NM_000372.5(TYR):c.572del (p.Gly191fs)

dbSNP: rs61754361

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000003988	SCV000597785	pathogenic	Tyrosinase-negative oculocutaneous albinism	2015-10-23	criteria provided, single submitter	clinical testing
GeneDx	RCV000085954	SCV001764098	pathogenic	not provided	2021-05-17	criteria provided, single submitter	clinical testing	Frameshift 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: 1905879)
Genome-Nilou Lab	RCV000003988	SCV001821932	pathogenic	Tyrosinase-negative oculocutaneous albinism	2021-07-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085954	SCV002246683	pathogenic	not provided	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly191Aspfs*35) 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 (rs61754361, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with oculocutaneous albinism (PMID: 1905879). ClinVar contains an entry for this variant (Variation ID: 99570). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003460782	SCV004207599	pathogenic	SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2023-06-25	criteria provided, single submitter	clinical testing
OMIM	RCV000003988	SCV000024154	pathogenic	Tyrosinase-negative oculocutaneous albinism	1991-07-01	no assertion criteria provided	literature only
Retina International	RCV000085954	SCV000118097	not provided	not provided		no assertion provided	not provided
PreventionGenetics, part of Exact Sciences	RCV004739351	SCV005344540	pathogenic	TYR-related disorder	2024-08-12	no assertion criteria provided	clinical testing	The TYR c.572delG variant is predicted to result in a frameshift and premature protein termination (p.Gly191Aspfs*35). This variant has been reported as causative for autosomal recessive oculocutaneous albinism (Oetting et al. 1991. PubMed ID: 1905879; King et al. 2003. PubMed ID: 13680365). This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in TYR are expected to be pathogenic, and this variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/99570). Given the evidence, we interpret this variant as pathogenic.