ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.1607T>C (p.Val536Ala) (rs138427376)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER _CC_NCGL, University of Washington RCV000029352 SCV000190070 uncertain significance Wilson disease 2014-06-01 criteria provided, single submitter research Low GERP score may suggest that this variant belongs in a lower pathogenicity class
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000374856 SCV000331695 benign not specified 2016-05-02 criteria provided, single submitter clinical testing
GeneDx RCV000514302 SCV000564676 uncertain significance not provided 2018-12-20 criteria provided, single submitter clinical testing The V536A variant in the ATP7B gene has been reported previously in association with Wilson disease; however, clinical information was not provided nor was information regarding the presence of a second variant in this individual (Davies et al., 2008). The V536A variant is observed in 296/25,790 (1.1%) alleles from individuals of Finnish background and 939/276,998 (0.39%) total alleles, including two unrelated homozygous individuals, in large population cohorts (Lek et al., 2016). The V536A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret V536A as a variant of uncertain significance.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514302 SCV000609818 likely benign not provided 2017-09-06 criteria provided, single submitter clinical testing
Invitae RCV000029352 SCV000626830 benign Wilson disease 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000514302 SCV000694399 uncertain significance not provided 2016-08-11 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.1607T>C (p.Val536Ala) variant involves the alteration of a non-conserved nucleotide. The altered amino acid is located in the heavy metal-associated domain. 3/5 in silico tools predict a benign outcome for this variant. This variant was found in 360/120802 control chromosomes, predominantly observed in the European (Finnish) subpopulation at a frequency of 0.0128515 (85/6614) without homozygous occurrences. This frequency is about 2.4 times the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006), suggesting this is possibly a benign polymorphism found primarily in the populations of European (Finnish) origin. This variant has been reported in at least one WD patient without strong evidence for pathogenicity (Davies_2008) and one patient with ADHD; this gene has not been strongnly established as a candidate gene for this phenotype (Lyon_2011). One Medical Center by reseach has classified this variant as VUS. Taken together, this variant is classified as VUS-possibly benign.
Counsyl RCV000029352 SCV000796670 likely benign Wilson disease 2017-12-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000514302 SCV001150662 uncertain significance not provided 2019-05-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000029352 SCV001268684 uncertain significance Wilson disease 2018-07-10 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GenomeConnect, ClinGen RCV000029352 SCV000606967 not provided Wilson disease no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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