ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.71G>A (p.Cys24Tyr)

gnomAD frequency: 0.00001  dbSNP: rs373333305
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001917604 SCV002164524 pathogenic not provided 2024-11-24 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 24 of the TYR protein (p.Cys24Tyr). This variant is present in population databases (rs373333305, gnomAD 0.0009%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 18701257, 31077556, 31199599, 32552135). 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: 1390436). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt TYR protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001917604 SCV002504231 pathogenic not provided 2022-01-17 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26165494, 18701257, 31077556, 31199599, 32725903)
Baylor Genetics RCV004571547 SCV005055659 pathogenic SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN 2023-11-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004587236 SCV005076974 pathogenic Oculocutaneous albinism 2024-04-08 criteria provided, single submitter clinical testing Variant summary: TYR c.71G>A (p.Cys24Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251472 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.71G>A has been reported in the literature in multiple individuals affected with Oculocutaneous Albinism (e.g., Wei_2022). These data indicate that the variant is very likely to be associated with disease. The following publication was ascertained in the context of this evaluation (PMID: 34838614). ClinVar contains an entry for this variant (Variation ID: 1390436). Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005006165 SCV005631903 pathogenic Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN 2024-04-09 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004741128 SCV005358566 pathogenic TYR-related disorder 2024-07-29 no assertion criteria provided clinical testing The TYR c.71G>A variant is predicted to result in the amino acid substitution p.Cys24Tyr. This variant has been reported in the compound heterozygous state in individuals with oculocutaneous albinism (Wang et al. 2009. PubMed ID: 18701257; Zhong et al. 2019. PubMed ID: 31077556; Lin et al. 2019. PubMed ID: 31199599). Alternate substitutions of this amino acid (p.Cys24Arg and p.Cys24Ser) have also been reported in individuals with oculocutaneous albinism (Wei et al. 2010. PubMed ID: 19865097; Table S1, Lasseaux et al. 2018. PubMed ID: 29345414). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Given the evidence, we interpret this variant as pathogenic.

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