Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780929 | SCV000918589 | uncertain significance | not specified | 2017-10-04 | criteria provided, single submitter | clinical testing | Variant summary: The ATP7B c.3749C>G (p.Ala1250Gly) variant causes a missense change involving the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 11/278196 control chromosomes (gnomAD and Coffey_2013) at a frequency of 0.0000395, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). 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. |
Fulgent Genetics, |
RCV001830673 | SCV002783184 | uncertain significance | Wilson disease | 2022-01-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001830673 | SCV003442231 | uncertain significance | Wilson disease | 2022-09-26 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1250 of the ATP7B protein (p.Ala1250Gly). This variant is present in population databases (rs372042739, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. ClinVar contains an entry for this variant (Variation ID: 633067). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Natera, |
RCV001830673 | SCV002086796 | uncertain significance | Wilson disease | 2020-02-25 | no assertion criteria provided | clinical testing |