ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.1259A>G (p.His420Arg)

dbSNP: rs2135324283
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001555815 SCV001777285 likely pathogenic not provided 2020-02-17 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge in individuals with oculocutaneous albinism; However, the H420R variant has been reported in mice and has been used as a functional model of OCA1B (Onojafe et al., 2011); This variant is associated with the following publications: (PMID: 24984260, 21968110, 29702637)
Labcorp Genetics (formerly Invitae), Labcorp RCV001555815 SCV002144110 uncertain significance not provided 2021-08-04 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 420 of the TYR protein (p.His420Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TYR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1193414). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV005005260 SCV005631388 likely pathogenic Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN 2024-04-07 criteria provided, single submitter clinical testing

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