ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.164G>A (p.Cys55Tyr)

gnomAD frequency: 0.00001  dbSNP: rs28940879
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000003993 SCV000597782 pathogenic Tyrosinase-negative oculocutaneous albinism 2016-03-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763288 SCV000893935 pathogenic Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; Ocular albinism with congenital sensorineural hearing loss; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN 2018-10-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000778345 SCV000914545 pathogenic Oculocutaneous albinism 2017-08-30 criteria provided, single submitter clinical testing The TYR c.164G>A (p.Cys55Tyr) missense variant has been reported in at least four studies in which it is found in a compound heterozygous state in at least eight individuals with oculocutaneous albinism (OA), two of whom were diagnosed with OA type 1B, four with OA type 1A, and two remained unspecified (Fukai et al. 1995; Hutton et al. 2008; Wei et al. 2010; Lin et al. 2014). The variant was also reported in one individual with OA in a heterozygous state with no second allele detected (Wei et al. 2010). One of the compound heterozygotes was heterozygous for the p.Cys55Tyr variant in trans with a complex allele [p.Arg402Gln;p.Ser192Tyr], which has been associated with temperature sensitive catalytic activity. The p.Cys55Tyr variant was also reported in a heterozygous state in this individual's unaffected mother (Fukai et al. 1995). Control data are unavailable for the p.Cys55Tyr variant, which is reported at a frequency of 0.00062 in the East Asian population of the Genome Aggregation Database. This is based on one allele only in a region of good sequence coverage so the variant can be assumed to be rare. Based on the evidence, the p.Cys55Tyr variant is classified as pathogenic for oculocutaneous albinism. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Genome-Nilou Lab RCV000003993 SCV001821921 pathogenic Tyrosinase-negative oculocutaneous albinism 2021-07-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000085930 SCV002224497 pathogenic not provided 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 55 of the TYR protein (p.Cys55Tyr). This variant is present in population databases (rs28940879, gnomAD 0.06%). This missense change has been observed in individuals with oculocutaneous albinism (PMID: 18463683, 19865097, 31077556). ClinVar contains an entry for this variant (Variation ID: 3790). 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%. For these reasons, this variant has been classified as Pathogenic.
MGZ Medical Genetics Center RCV002288461 SCV002581366 pathogenic Oculocutaneous albinism type 1B 2022-02-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV003466801 SCV004207613 pathogenic SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN 2023-11-09 criteria provided, single submitter clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc RCV004795372 SCV005416021 pathogenic Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B criteria provided, single submitter clinical testing PM2_Supporting+PM3_VeryStrong+PP4+PP3_Moderate
Fulgent Genetics, Fulgent Genetics RCV005003327 SCV005631909 pathogenic Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN 2024-03-12 criteria provided, single submitter clinical testing
OMIM RCV000003993 SCV000024159 pathogenic Tyrosinase-negative oculocutaneous albinism 1991-02-01 no assertion criteria provided literature only
Retina International RCV000085930 SCV000118073 not provided not provided no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.