ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.1708-5T>G (rs770829226)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589652 SCV000694403 pathogenic Wilson disease 2016-12-30 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.1708-5T>G variant involves the alteration of a conserved intronic nucleotide, which 4/5 splice prediction tools predict an affect on splicing. A functional study, Shimizu_1995 supports these predictions with the observation of the variant causing exon 5 skipping. The variant of interest was observed in controls with an allele frequency of 1/120756, which does not exceed the estimated maximal expected allele frequency for a pathogenic ATP7B variant of 1/185. Multiple publications report the variant in Wilson Disease patients as homozygotes and compound heterozygotes, predominantly in Japanese individuals. Multiple databases have cited the variant as "pathogenic." Therefore, the variant of interest has been classified as "Pathogenic."
Fulgent Genetics,Fulgent Genetics RCV000589652 SCV000894017 likely pathogenic Wilson disease 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000589652 SCV001215055 pathogenic Wilson disease 2020-06-03 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the ATP7B gene. It does not directly change the encoded amino acid sequence of the ATP7B protein. This variant is present in population databases (rs770829226, ExAC 0.01%). This variant has been observed to be homozygous in or in combination with another ATP7B variant individuals affected with Wilson disease (PMID: 10790207, 8526905, 28507923, 11721763, 21707886). ClinVar contains an entry for this variant (Variation ID: 495402). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 8526905). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000589652 SCV000790754 pathogenic Wilson disease 2017-04-06 no assertion criteria provided clinical testing
Natera, Inc. RCV000589652 SCV001463846 pathogenic Wilson disease 2020-09-16 no assertion criteria provided clinical testing

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