Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000195126 | SCV000246653 | pathogenic | Menkes kinky-hair syndrome | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003765212 | SCV004571516 | pathogenic | Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3 | 2023-03-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 210401). Disruption of this splice site has been observed in individuals with Menkes disease (MD) (PMID: 8981948, 21494555). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 7 of the ATP7A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATP7A are known to be pathogenic (PMID: 11241493, 20652413). |
Clinical Genetics Laboratory, |
RCV004696867 | SCV005199646 | pathogenic | not provided | 2023-09-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV004696867 | SCV005201694 | pathogenic | not provided | 2023-07-28 | criteria provided, single submitter | clinical testing | Reported previously in a patient with classic Menkes disease; parental testing not performed (Tumer et al., 1997); Published functional studies in vivo demonstrated that the variant created a cryptic splice site resulting in a frameshift; wildtype transcript was not identified (Skjorringe et al., 2011); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 8981948, 21494555) |
Inherited Neuropathy Consortium Ii, |
RCV000195126 | SCV004011890 | uncertain significance | Menkes kinky-hair syndrome | 2016-01-06 | no assertion criteria provided | literature only |