Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000317010 | SCV000330108 | pathogenic | not provided | 2017-07-07 | criteria provided, single submitter | clinical testing | The R601X pathogenic variant in the ANKRD11 gene has been reported previously as a de-novo finding in an individual with submucous cleft hard palate, learning disability, abnormality of the lip, microcephaly, mild conductive hearing impairment, bifid uvula, and widely-spaced maxillary central incisors (Fitzgerald et al., 2015). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R601X variant was not observed in approximately 6500 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 R601X as a pathogenic variant. |
| Invitae | RCV001251665 | SCV003522003 | pathogenic | KBG syndrome | 2022-06-02 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg601*) in the ANKRD11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANKRD11 are known to be pathogenic (PMID: 21782149, 25125236, 25413698, 25652421). This premature translational stop signal has been observed in individual(s) with ANKRD11-related conditions (PMID: 25533962, 27667800). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 280209). For these reasons, this variant has been classified as Pathogenic. |
| Centre de Biologie Pathologie Génétique, |
RCV001251665 | SCV001427405 | pathogenic | KBG syndrome | 2019-01-01 | no assertion criteria provided | clinical testing |