ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.4063G>A (p.Gly1355Ser)

dbSNP: rs1555282751
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670965 SCV000795895 uncertain significance Wilson disease 2017-11-29 criteria provided, single submitter clinical testing
Invitae RCV000670965 SCV001228810 uncertain significance Wilson disease 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 1355 of the ATP7B protein (p.Gly1355Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Wilson disease (PMID: 8938442). ClinVar contains an entry for this variant (Variation ID: 555192). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV000670965 SCV002027147 uncertain significance Wilson disease 2021-09-05 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000670965 SCV004825141 likely pathogenic Wilson disease 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 1355 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Although functional studies have not been reported for this variant, it alters a conserved glycine residue in the transmembrane domain M6 of the ATP7B protein (a.a 1352 - 1375), a highly conserved region that is considered to be important for ATP7B protein function (PMID: 35245129; ClinVar). This variant has been observed in two individuals affected with autosomal recessive Wilson disease (PMID: 8938442, 15967699), including one individual in the compound heterozygous state with a second pathogenic ATP7B variant (PMID: 8938442). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.

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