ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.1621G>A (p.Glu541Lys)

gnomAD frequency: 0.00014  dbSNP: rs187046823
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000487499 SCV000109878 uncertain significance not provided 2013-01-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000487499 SCV000574959 uncertain significance not provided 2019-05-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000487499 SCV000694401 uncertain significance not provided 2016-09-21 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.1621G>A (p.Glu541Lys) variant involves the alteration of a non-conserved nucleotide located in the HMA domain (heavy-metal-associated) domain of ATP7B. 4/4 in silico tools predict a benign outcome for this substitution (SNPs&GO not captured due to low reliability index). This variant was found in 16/122754 control chromosomes at a frequency of 0.0001303, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). To our knowledge, the variant was not reported in affected individuals at the time of classification. One clinical diagnostic laboratory classified this variant as uncertain significance. Due to 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 RCV000670794 SCV000795693 uncertain significance Wilson disease 2017-11-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000670794 SCV002027172 uncertain significance Wilson disease 2021-09-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000670794 SCV002786372 uncertain significance Wilson disease 2024-03-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000670794 SCV003278194 uncertain significance Wilson disease 2022-10-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 541 of the ATP7B protein (p.Glu541Lys). This variant is present in population databases (rs187046823, gnomAD 0.02%). This missense change has been observed in individual(s) with Wilson disease (PMID: 23235335). ClinVar contains an entry for this variant (Variation ID: 92386). 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 not expected to disrupt ATP7B protein function. Experimental studies have shown that this missense change does not substantially affect ATP7B function (PMID: 17919502). 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000487499 SCV004226452 uncertain significance not provided 2023-03-20 criteria provided, single submitter clinical testing PM2
All of Us Research Program, National Institutes of Health RCV000670794 SCV004846333 uncertain significance Wilson disease 2024-09-23 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 541 of the ATP7B protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with Wilson disease (PMID: 23518715). This variant has been identified in 27/280880 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017388 SCV004848322 likely benign not specified 2020-06-11 criteria provided, single submitter clinical testing This variant was reported in at least two individuals with Wilson disease, however a second variant was not reported (Coffey 2013, Collet 2018). Variant is present in 0.01% (21/12624) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). It is listed in ClinVar as Uncertain Significance by 4 clinical laboratories (Variation ID 92386). Three mammals harbor a Lysine (Lys) at this amino acid position. For this reason, the variant is classified as likely benign. ACMG/AMP Criteria applied: BP4_Strong.
Natera, Inc. RCV000670794 SCV001463850 uncertain significance Wilson disease 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.