Submissions for variant NM_000372.5(TYR):c.1255G>A (p.Gly419Arg)

gnomAD frequency: 0.00001  dbSNP: rs61754392

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome-Nilou Lab	RCV001554298	SCV001774839	pathogenic	Oculocutaneous albinism type 1	2021-08-08	criteria provided, single submitter	clinical testing	We found this variant in a 1-year-old boy with OCA1 in the homozygous state.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085914	SCV002242843	pathogenic	not provided	2024-09-17	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 419 of the TYR protein (p.Gly419Arg). This variant is present in population databases (rs61754392, gnomAD 0.04%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 16907708, 19865097, 27734839, 28266639, 32115698). 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: 3792). 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 80%. Experimental studies have shown that this missense change affects TYR function (PMID: 20861851). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000085914	SCV002588337	pathogenic	not provided	2022-04-29	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a lack of tyrosine hydroxylase and DOPA oxidase compared to wild type (Chaki et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 1943686, 20861851, 28507374, 30996339, 28266639, 30868578, 33800529)
Fulgent Genetics, Fulgent Genetics	RCV002490305	SCV002810941	pathogenic	Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2024-05-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000085914	SCV004010110	pathogenic	not provided	2023-06-01	criteria provided, single submitter	clinical testing	TYR: PS4, PM2, PP1:Moderate, PP3, PP4, PS3:Supporting
Baylor Genetics	RCV003460420	SCV004207542	pathogenic	SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2024-03-16	criteria provided, single submitter	clinical testing
OMIM	RCV000003995	SCV000024161	pathogenic	Tyrosinase-negative oculocutaneous albinism	1991-02-01	no assertion criteria provided	literature only
Retina International	RCV000085914	SCV000118057	not provided	not provided		no assertion provided	not provided
University of Washington Center for Mendelian Genomics, University of Washington	RCV000755080	SCV000882898	likely pathogenic	Nonsyndromic Oculocutaneous Albinism	2017-03-07	no assertion criteria provided	research
Institute of Biotechnology and Microbiology, Bacha Khan University, Charsadda	RCV000003995	SCV004174815	pathogenic	Tyrosinase-negative oculocutaneous albinism		no assertion criteria provided	research