Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480677 | SCV000570534 | likely pathogenic | not provided | 2016-05-31 | criteria provided, single submitter | clinical testing | The c.1673delC variant in the ZNF469 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1673delC variant causes a frameshift starting with codon Alanine 558, changes this amino acid to a Valine residue, and creates a premature Stop codon at position 26 of the new reading frame, denoted p.Ala558ValfsX26. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1673delC variant was not observed in approximately 2,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1673delC as a strong candidate for a pathogenic variant; however the possibility that it may be a rare benign variant cannot be excluded. |
| Invitae | RCV000480677 | SCV004332002 | pathogenic | not provided | 2023-10-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala558Valfs*26) in the ZNF469 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZNF469 are known to be pathogenic (PMID: 23642083, 23680354). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZNF469-related conditions. ClinVar contains an entry for this variant (Variation ID: 421353). For these reasons, this variant has been classified as Pathogenic. |