ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.832C>T (p.Arg278Ter) (rs62645904)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000502958 SCV000597789 pathogenic Tyrosinase-negative oculocutaneous albinism 2016-07-25 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000085974 SCV000854931 pathogenic not provided 2017-08-10 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762869 SCV000893249 pathogenic Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; Albinism, ocular, with sensorineural deafness; Skin/hair/eye pigmentation, variation in, 3 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778349 SCV000914549 pathogenic Oculocutaneous albinism 2018-11-01 criteria provided, single submitter clinical testing The TYR c.832C>T (p.Arg278Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Arg278Ter variant is a well-documented variant that has been reported in individuals with oculocutaneous albinism (OA) in multiple ethnic groups. Across a selection of the available literature, the p.Arg278Ter variant has been identified in 28 probands in a homozygous state, six probands in a compound heterozygous state, and three probands in a heterozygous state (Tripathi et al. 1993; Gershoni-Baruch et al. 1994; Goto et al. 2004; Sundaresan et al. 2004; Chaki et al. 2005; Renugadevi et al. 2010; Park et al. 2012; Wei et al. 2013; Wang et al. 2015). The p.Arg278Ter variant was absent from 137 control individuals and is reported at a frequency of 0.00115 in the South Asian population of the Exome Aggregation Consortium. Haplotype analysis suggested that p.Arg278Ter may be a founder variant (Chaki et al. 2005; Jaworek et al. 2012). Based on the collective evidence and the potential impact of stop-gained variants, the p.Arg278Ter 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.
Invitae RCV000085974 SCV001380185 pathogenic not provided 2019-11-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg278*) in the TYR gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs62645904, ExAC 0.1%). This variant has been reported in many families and individuals affected with oculocutaneous albinism (PMID: 27829221, 23324268, 26165494, 28266639). ClinVar contains an entry for this variant (Variation ID: 99583). Loss-of-function variants in TYR are known to be pathogenic (PMID: 23504663). For these reasons, this variant has been classified as Pathogenic.
Retina International RCV000085974 SCV000118117 not provided not provided no assertion provided not provided
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000502958 SCV000778806 pathogenic Tyrosinase-negative oculocutaneous albinism 2018-06-19 no assertion criteria provided clinical testing The observed variant c.832C>T (p.Arg278Ter) is not reported in 1000 Genomes and its minor allele frequency in ExAC databases is 0.0002. The variant is found to be disease-causing by MutationTaster2. The reference codon is conserved across species. The observed variant has previously been reported in patients affected with oculocutaneous albinism (Wang et al., 2015)
University of Washington Center for Mendelian Genomics, University of Washington RCV000755071 SCV000882889 likely pathogenic Nonsyndromic Oculocutaneous Albinism 2017-03-07 no assertion criteria provided research

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