Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002401012 | SCV002708002 | uncertain significance | Inborn genetic diseases | 2019-09-26 | criteria provided, single submitter | clinical testing | The p.P540A variant (also known as c.1618C>G), located in coding exon 5 of the ATP7A gene, results from a C to G substitution at nucleotide position 1618. The proline at codon 540 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV003097014 | SCV003487982 | likely benign | Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3 | 2023-05-24 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003988006 | SCV004804219 | uncertain significance | not specified | 2024-01-08 | criteria provided, single submitter | clinical testing | Variant summary: ATP7A c.1618C>G (p.Pro540Ala) results in a non-conservative amino acid change located in the Heavy metal-associated domain, HMA (IPR006121) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.1e-05 in 183475 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1618C>G in individuals affected with Menkes Kinky-Hair Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1776536). Based on the evidence outlined above, the variant was classified as uncertain significance. |