Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002389263 | SCV002699119 | uncertain significance | Inborn genetic diseases | 2022-02-10 | criteria provided, single submitter | clinical testing | The c.1400C>G (p.T467S) alteration is located in exon 5 (coding exon 4) of the ATP7A gene. This alteration results from a C to G substitution at nucleotide position 1400, causing the threonine (T) at amino acid position 467 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003095095 | SCV003488566 | uncertain significance | Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3 | 2021-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 467 of the ATP7A protein (p.Thr467Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATP7A-related conditions. 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 ATP7A 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. |