ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.1111A>T (p.Asn371Tyr)

gnomAD frequency: 0.00001  dbSNP: rs61754386
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000085896 SCV000567323 pathogenic not provided 2019-07-09 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect with loss of enzyme activity (Mondal et al., 2016); This variant is associated with the following publications: (PMID: 10987646, 23085273, 28976636, 28451379, 27537549, 31589614)
Genome-Nilou Lab RCV001588916 SCV001821961 likely pathogenic Tyrosinase-negative oculocutaneous albinism 2021-07-22 criteria provided, single submitter clinical testing
Invitae RCV000085896 SCV002229123 pathogenic not provided 2023-11-06 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 371 of the TYR protein (p.Asn371Tyr). This variant is present in population databases (rs61754386, gnomAD 0.004%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 10987646, 28976636). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 99534). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects TYR function (PMID: 27537549). This variant disrupts the p.Asn371 amino acid residue in TYR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1676041, 8434585). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Retina International RCV000085896 SCV000118039 not provided not provided no assertion provided not provided

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