ClinVar Miner

Submissions for variant NM_001290043.2(TAP2):c.1417G>A (p.Val473Ile)

gnomAD frequency: 0.00005  dbSNP: rs765178638
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788754 SCV000927983 uncertain significance not provided 2018-10-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001056446 SCV001220889 uncertain significance MHC class I deficiency 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 473 of the TAP2 protein (p.Val473Ile). This variant is present in population databases (rs765178638, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 636814). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001056446 SCV001468442 uncertain significance MHC class I deficiency 2021-03-30 criteria provided, single submitter clinical testing TAP2 NM_000544.3 exon 8 p.Val473Ile (c.1417G>A): This variant has not been reported in the literature but is present in 0.009% (1/10262) of Ashkenazi Jewish alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/6-32798439-C-T?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:636814). Of note, 3 species carry this variant Isoleucine (Ile) as wild type (Prarie Vole, Chinese Hamster, Lizard); however, evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Johns Hopkins Genomics, Johns Hopkins University RCV001056446 SCV001711948 uncertain significance MHC class I deficiency 2021-05-28 criteria provided, single submitter clinical testing TAP2 c.1417G>A (rs765178638) is rare (<0.1%) in a large population dataset (gnomAD: 12/277972 total alleles; 0.004%; no homozygotes) and has not been reported in the literature, to our knowledge. This variant has been reported in ClinVar. Of three bioinformatics tools queried, two predict that the substitution would be tolerated, while one predicts that it would be damaging. The valine residue at this position is evolutionarily conserved in many of the species assessed, however an isoleucine is present at this position in a subset of species. We consider the clinical significance of TAP2 c.1417G>A to be uncertain at this time.
Breakthrough Genomics, Breakthrough Genomics RCV000788754 SCV005188890 uncertain significance not provided criteria provided, single submitter not provided

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