ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.649C>T (p.Arg217Trp) (rs63159160)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763290 SCV000893937 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
GeneDx RCV000085962 SCV000491313 likely pathogenic not provided 2018-04-30 criteria provided, single submitter clinical testing The R217W variant in the TYR gene has been reported previously in association with autosomal recessive oculocutaneous albinism type 1 when present in the homozygous state or when in trans with another disease-causing variant (King et al., 2003; Hutton et al., 2008; Rosenmann et al., 2009; Ghodsinejad et al., 2014). The R217W variant is observed in 53/276,474 (0.019%) total alleles in large population cohorts (Lek et al., 2016). The R217W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. However, missense variants at the same residue (R217G, R217Q) and nearby residues (R212T, R212K, L216M, W218R, E219K, E221K, I222T) have been reported in association with oculocutaneous albinism type 1 (Oetting et al., 1993; Spritz et al., 1997; King et al., 2003; Hutton et al., 2008; Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret R217W as a likely pathogenic variant.
OMIM RCV000003999 SCV000024165 pathogenic Tyrosinase-negative oculocutaneous albinism 1992-07-15 no assertion criteria provided literature only
Retina International RCV000085962 SCV000118105 not provided not provided no assertion provided not provided
University of Washington Center for Mendelian Genomics,University of Washington RCV000755070 SCV000882888 likely pathogenic Nonsyndromic Oculocutaneous Albinism 2017-03-07 no assertion criteria provided research

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