ClinVar Miner

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

dbSNP: rs776848753
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Total submissions: 7
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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 2022-11-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ATP7B function (PMID: 19937698). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP7B protein function. ClinVar contains an entry for this variant (Variation ID: 188908). This missense change has been observed in individual(s) with Wilson disease (PMID: 10544227, 21610751, 24094725). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1363 of the ATP7B protein (p.Ser1363Phe).
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.
Genome-Nilou Lab RCV000169268 SCV001977212 pathogenic Wilson disease 2021-08-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV000169268 SCV004216427 pathogenic Wilson disease 2023-05-04 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV003480071 SCV004226637 pathogenic not provided 2022-08-23 criteria provided, single submitter clinical testing PP3, PP4, PM2, PM3_strong, PS4_moderate
Revvity Omics, Revvity Omics RCV000169268 SCV004238413 pathogenic Wilson disease 2023-06-12 criteria provided, single submitter clinical testing

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