Submissions for variant NM_000372.5(TYR):c.1352A>G (p.Tyr451Cys)

gnomAD frequency: 0.00022  dbSNP: rs376823382

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000626674	SCV000747377	likely pathogenic	Albinism; Abnormal retinal morphology; Strabismus; Abnormal optic nerve morphology; Horizontal nystagmus; Hypopigmentation of the skin; Ocular albinism; Fair hair	2017-01-01	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001197897	SCV001368680	likely pathogenic	Tyrosinase-negative oculocutaneous albinism	2019-03-19	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PM3,PP3,PP5.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001860478	SCV002274850	pathogenic	not provided	2024-11-15	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 451 of the TYR protein (p.Tyr451Cys). This variant is present in population databases (rs376823382, gnomAD 0.05%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 20861488, 34897530). 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: 523363). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt TYR protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
MGZ Medical Genetics Center	RCV002289915	SCV002581775	likely pathogenic	Oculocutaneous albinism type 1B	2022-08-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001860478	SCV005041600	likely pathogenic	not provided	2024-04-01	criteria provided, single submitter	clinical testing	TYR: PM3:Strong, PM2, PP4
Fulgent Genetics, Fulgent Genetics	RCV005004280	SCV005631392	likely pathogenic	Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2024-03-25	criteria provided, single submitter	clinical testing