ClinVar Miner

Submissions for variant NM_000372.4(TYR):c.1209G>T (p.Arg403Ser) (rs104894316)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000085911 SCV000491314 likely pathogenic not provided 2016-07-22 criteria provided, single submitter clinical testing The R403S variant in the TYR gene has been reported previously in individuals who underwent genetic testing for oculocutaneous albinism type 1 (Opitz et al., 2004; Oetting et al., 1993; Hutton et al., 2008). The R403S variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R403S variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved; however, in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues (E398V, E398G, W400L, W400C, R402G, R402L, H404N, H404P, R405L, P406L, Q408H) have been reported in the Human Gene Mutation Database in association with oculocutaneous albinism type 1 (Stenson et al., 2014), supporting the functional importance of this region of the protein. The R403S variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
OMIM RCV000004004 SCV000024170 pathogenic Tyrosinase-negative oculocutaneous albinism 1992-07-15 no assertion criteria provided literature only
Retina International RCV000085911 SCV000118054 not provided not provided no assertion provided not provided

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