ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.823G>T (p.Val275Phe) (rs104894314)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000192471 SCV000249343 pathogenic Tyrosinase-negative oculocutaneous albinism 2015-02-04 criteria provided, single submitter clinical testing
GeneDx RCV000085973 SCV000329587 pathogenic not provided 2018-12-07 criteria provided, single submitter clinical testing The V275F pathogenic variant in the TYR gene has been reported previously in association with oculocutaneous albinism, when present in the homozygous state or when in trans with another pathogenic variant (Giebel et al., 1991; Camand et al., 2001; Hutton and Spritz, 2008; Lasseaux et al., 2018). The V275F variant is observed in 26/126,424 (0.0206%) alleles from individuals of non-Finnish European background in large population cohorts and no individuals were reported to be homozygous (Lek et al., 2016). The V275F variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. We interpret V275F as a pathogenic variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000085973 SCV000332569 pathogenic not provided 2016-12-13 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762868 SCV000893248 likely 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 RCV000778348 SCV000914548 pathogenic Oculocutaneous albinism 2018-08-14 criteria provided, single submitter clinical testing The TYR c.823G>T (p.Val275Phe) missense variant has been reported in at least three studies in which it is found in a total of 23 individuals with a clinical diagnosis of oculocutaneous albinism type 1 (OCA1) (of whom 20 are related), in a compound heterozygous state with either missense or frameshift variants on the second allele. The p.Val275Phe variant has also been found in a heterozygous state in one additional individual with a clinical diagnosis of OCA1 (Giebel et al. 1991; King et al. 2003; Hutton and Spritz 2008). Of the 23 affected compound heterozygous individuals, 19 were affected with OCA type 1B, and four were affected with OCA type 1A. The p.Val275Phe variant was also identified in a heterozygous state in an unspecified number of unaffected family members of one of the probands from Giebel et al. (1991). Quantitative assay of tyrosinase in freshly epilated anagen hairbulbs from one of the probands in Giebel et al. (1991) showed low activity at approximately 6% of normal range, and another showed no detectable activity. The variant was absent from 30 typically-pigmented controls (Giebel et al. 1991) but is reported at a frequency of 0.000206 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the collective evidence, the p.Val275Phe 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.
OMIM RCV000003972 SCV000024137 pathogenic Oculocutaneous albinism type 1B 2020-02-03 no assertion criteria provided literature only
Retina International RCV000085973 SCV000118116 not provided not provided no assertion provided not provided

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