ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.1039T>C (p.Phe347Leu)

dbSNP: rs2135281765
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV001775444 SCV002012352 likely pathogenic Tyrosinase-negative oculocutaneous albinism 2021-10-02 criteria provided, single submitter clinical testing It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed in trans with a pathogenic variant (NM_000372.4: c.929dup) as compound heterozygous (3billion dataset, PM3). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.916, 3Cnet: 0.958, PP3). Patient's phenotype is considered compatible with Albinism, Oculicutaneous, Type 1A (3billion dataset, PP4). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Labcorp Genetics (formerly Invitae), Labcorp RCV003660901 SCV004375984 likely pathogenic not provided 2023-02-14 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 347 of the TYR protein (p.Phe347Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 32901917). 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: 1320271). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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