ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.4301C>T (p.Thr1434Met) (rs60986317)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000251030 SCV000052027 likely benign not specified 2018-02-27 criteria provided, single submitter clinical testing Variant summary: ATP7B c.4301C>T (p.Thr1434Met) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0019 in 120828 control chromosomes, predominantly at a frequency of 0.0057 within the African or African-American subpopulation in the ExAC database. The observed variant frequency within African or African-American control individuals in the ExAC database is slightly higher than the estimated maximal expected allele frequency for a pathogenic variant in ATP7B causing Wilson Disease phenotype (0.0054), suggesting that the variant is possibly a benign polymorphism found primarily in populations of African or African-American origin. c.4301C>T has been reported in the literature in individuals affected with Wilson Disease or psychiatric disease in homozygous or heterozygous state. However, co-occurrences with other pathogenic variant have been reported (ATP7B homozygous c.3809A>G, p.N1270S), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Braiterman_2011, Hsi_2003). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224611 SCV000280605 uncertain significance not provided 2015-02-06 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
PreventionGenetics,PreventionGenetics RCV000251030 SCV000301725 benign not specified criteria provided, single submitter clinical testing
Invitae RCV000224611 SCV000626863 likely benign not provided 2019-03-04 criteria provided, single submitter clinical testing
Counsyl RCV000029379 SCV000800724 uncertain significance Wilson disease 2017-04-18 criteria provided, single submitter clinical testing
Mendelics RCV000029379 SCV001139345 uncertain significance Wilson disease 2019-05-28 criteria provided, single submitter clinical testing

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