Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001241547 | SCV001414571 | uncertain significance | Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3 | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1358 of the ATP7A protein (p.Asn1358Ser). 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. ClinVar contains an entry for this variant (Variation ID: 966789). 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 expected to disrupt ATP7A protein function with a positive predictive value of 95%. 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. |
| Laboratory of Medical Genetics, |
RCV001828980 | SCV002577456 | likely benign | Menkes kinky-hair syndrome | 2022-01-17 | criteria provided, single submitter | clinical testing | BS2, PM2, PP3 |
| Ambry Genetics | RCV002322147 | SCV002628198 | uncertain significance | Inborn genetic diseases | 2020-02-20 | criteria provided, single submitter | clinical testing | The p.N1358S variant (also known as c.4073A>G), located in coding exon 20 of the ATP7A gene, results from an A to G substitution at nucleotide position 4073. The asparagine at codon 1358 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Centre de Biologie Pathologie Génétique, |
RCV001252421 | SCV001428177 | likely benign | Intellectual disability | 2019-01-01 | no assertion criteria provided | clinical testing | |
| Natera, |
RCV001828980 | SCV002089106 | uncertain significance | Menkes kinky-hair syndrome | 2020-08-07 | no assertion criteria provided | clinical testing |