ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs61754392
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Total submissions: 10
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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.
Invitae RCV000085914 SCV002242843 pathogenic not provided 2024-01-09 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). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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 2022-02-26 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 2023-10-28 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

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