ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.755T>G (p.Met252Arg)

dbSNP: rs1943262190
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001882806 SCV002194880 pathogenic not provided 2023-11-05 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 252 of the TYR protein (p.Met252Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 29345414; Invitae). 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: 1301877). 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%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001882806 SCV003805552 uncertain significance not provided 2022-08-18 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29345414, 35027574)
CeGaT Center for Human Genetics Tuebingen RCV001882806 SCV004010109 pathogenic not provided 2023-08-01 criteria provided, single submitter clinical testing TYR: PM3:Very Strong, PM2, PM5, PP4
Rare Disease Group, University of Exeter RCV002226431 SCV001984755 likely pathogenic Tyrosinase-negative oculocutaneous albinism no assertion criteria provided research

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