ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.4088C>T (p.Ser1363Phe) (rs776848753)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169268 SCV000220568 likely pathogenic Wilson disease 2014-08-01 criteria provided, single submitter literature only
Invitae RCV000169268 SCV001373016 pathogenic Wilson disease 2019-09-16 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 1363 of the ATP7B protein (p.Ser1363Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Wilson disease (PMID: 10544227, 21610751, 24094725). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 188908). This variant has been reported to affect ATP7B protein function (PMID: 19937698). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169268 SCV001572524 pathogenic Wilson disease 2021-04-14 criteria provided, single submitter clinical testing Variant summary: ATP7B c.4088C>T (p.Ser1363Phe) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246976 control chromosomes (gnomAD). c.4088C>T (p.Ser1363Phe) has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Wilson Disease (e.g. Loudianos_1999, Moller_2011, Mukherjee_2014). These data indicate that the variant is very likely to be associated with disease. Experimental evidence demonstrated the variant affects protein function (e.g. van den Berghe_2009). A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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