ClinVar Miner

Submissions for variant NM_000550.3(TYRP1):c.1067G>A (p.Arg356Gln)

gnomAD frequency: 0.00004  dbSNP: rs281865424
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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 RCV001851935 SCV002259721 pathogenic not provided 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 356 of the TYRP1 protein (p.Arg356Gln). This variant is present in population databases (rs281865424, gnomAD 0.01%). This missense change has been observed in individuals with oculocutaneous albinism (PMID: 16704458, 21739261, 28266639). This variant is also known as c.1066G>A. ClinVar contains an entry for this variant (Variation ID: 17596). 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 TYRP1 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002476990 SCV002777440 likely pathogenic Oculocutaneous albinism type 3; MELANESIAN BLOND HAIR 2024-06-16 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003390690 SCV004112004 pathogenic TYRP1-related disorder 2023-05-30 criteria provided, single submitter clinical testing The TYRP1 c.1067G>A variant is predicted to result in the amino acid substitution p.Arg356Gln. This variant has been reported in the homozygous and compound heterozygous state in individuals with oculocutaneous albinism (Rooryck et al. 2006. PubMed ID: 16704458; Shahzad et al. 2017. PubMed ID: 28266639; Zhang et al. 2011. PubMed ID: 21739261). This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-12702424-G-A). Given the evidence, we interpret c.1067G>A (p.Arg356Gln) as pathogenic.
GeneDx RCV001851935 SCV005396390 uncertain significance not provided 2024-05-01 criteria provided, single submitter clinical testing Observed with a second TYRP1 variant in unrelated patients in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes in some cases (PMID: 16704458, 21739261, 34838614); 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: 23862152, 28661582, 37956964, 35547362, 38542347, 30868578, 28266639, 34838614, 16704458, 21739261)
OMIM RCV000019162 SCV000039450 pathogenic Oculocutaneous albinism type 3 2006-06-01 no assertion criteria provided literature only
University of Washington Center for Mendelian Genomics, University of Washington RCV000755096 SCV000882914 likely pathogenic Nonsyndromic Oculocutaneous Albinism 2017-03-07 no assertion criteria provided research

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