ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.4213G>A (p.Gly1405Ser) (rs189601972)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513406 SCV000608685 likely pathogenic not provided 2017-04-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000513406 SCV000694465 uncertain significance not provided 2017-06-19 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.4213G>A (p.Gly1405Ser) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured). This variant was found in 4/120612 control chromosomes at a frequency of 0.0000332, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Counsyl RCV000670982 SCV000795914 uncertain significance Wilson disease 2017-11-30 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000513406 SCV000885051 uncertain significance not provided 2018-04-04 criteria provided, single submitter clinical testing The ATP7B c.4213G>A; p.Gly1405Ser variant (rs189601972), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 444316). This variant is found in the general population with an overall allele frequency of 0.004% (11/275580 alleles) in the Genome Aggregation Database. The glycine at codon 1405 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the p.Gly1405Ser variant is uncertain at this time.
Invitae RCV000670982 SCV000939130 uncertain significance Wilson disease 2018-09-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 1405 of the ATP7B protein (p.Gly1405Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs189601972, ExAC 0.009%). This variant has not been reported in the literature in individuals with ATP7B-related disease. ClinVar contains an entry for this variant (Variation ID: 444316). 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.

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