ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.1620C>T (p.Leu540=) (rs145798966)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000244316 SCV000301695 benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000244316 SCV000518709 likely benign not specified 2018-02-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000244316 SCV000602599 benign not specified 2016-11-29 criteria provided, single submitter clinical testing
Invitae RCV001086715 SCV000626831 benign Wilson disease 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000244316 SCV000694400 likely benign not specified 2018-05-07 criteria provided, single submitter clinical testing Variant summary: ATP7B c.1620C>T alters a non-conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 0.0014 in 279008 control chromosomes, predominantly at a frequency of 0.0024 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than expected for a pathogenic variant in ATP7B causing Wilson Disease (0.0014 vs 0.0054), allowing no conclusion about variant significance. The variant, c.1620C>T, has been reported in the literature in individuals affected with Wilson Disease (Cheng_2017, Dong_2016) but also in one patient with inherited cerebellar ataxia without Wilson disease, together with the likely pathogenic variant ATP7B c.2972C>T (p.Thr991Met)( Marelli_2016)(phase unknown). These reports do not provide unequivocal conclusions about association of the variant with Wilson Disease. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and with conflicting classifications (benign x2, likely benign x1, uncertain significance x1). Based on the evidence outlined above, the variant was classified as likely benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000590083 SCV000704531 uncertain significance not provided 2016-12-20 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000590083 SCV001150661 likely benign not provided 2019-06-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001086715 SCV001268683 uncertain significance Wilson disease 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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