Submissions for variant NM_000372.5(TYR):c.732_733del (p.Cys244_Asp245delinsTer)

dbSNP: rs61754368

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000085968	SCV000224202	pathogenic	not provided	2015-03-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000085968	SCV000617795	pathogenic	not provided	2024-05-09	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: 28771251, 28667292, 28976636, 28451379, 23504663, 1905879)
CeGaT Center for Human Genetics Tuebingen	RCV000085968	SCV001248570	pathogenic	not provided	2017-07-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000003990	SCV001821941	pathogenic	Tyrosinase-negative oculocutaneous albinism	2021-07-22	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000085968	SCV002022495	pathogenic	not provided	2020-04-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085968	SCV002235136	pathogenic	not provided	2024-12-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Cys244*) 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 (rs747193559, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 28667292, 28771251, 28976636). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 3787). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003460417	SCV004207607	pathogenic	SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2024-03-14	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005007817	SCV005631344	pathogenic	Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2024-01-29	criteria provided, single submitter	clinical testing
OMIM	RCV000003990	SCV000024156	pathogenic	Tyrosinase-negative oculocutaneous albinism	1991-07-01	no assertion criteria provided	literature only
Retina International	RCV000085968	SCV000118111	not provided	not provided		no assertion provided	not provided
PreventionGenetics, part of Exact Sciences	RCV004739288	SCV005350310	pathogenic	TYR-related disorder	2024-08-01	no assertion criteria provided	clinical testing	The TYR c.732_733delTG variant is predicted to result in premature protein termination (p.Cys244*). This variant has been reported in the compound heterozygous state in multiple individuals with oculocutaneous albinism (Oetting et al. 1991. PubMed ID: 1905879; Norman et al. 2017. PubMed ID: 28667292; Marti et al. 2017. PubMed ID: 28976636). This variant is reported in 0.0054% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in TYR are an established mechanism of disease. Given all the evidence, we interpret this variant as pathogenic.