Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000578602 | SCV000680773 | pathogenic | not provided | 2017-12-20 | criteria provided, single submitter | clinical testing | The R47X variant in the KIF11 gene has been reported previously as a de novo change in an individual with microcephaly, lymphedema, and chorioretinal dysplasia (Hazan et al., 2012). The R47X variant has also been reported in an individual with retinal detachment; however parental studies were not performed and there was limited additional clinical information provided (Robitaille et al., 2014). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R47X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R47X as a pathogenic variant. |
| Invitae | RCV000578602 | SCV003441541 | pathogenic | not provided | 2022-07-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 488844). This premature translational stop signal has been observed in individual(s) with KIF11-related conditions (PMID: 22653704). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg47*) in the KIF11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KIF11 are known to be pathogenic (PMID: 22284827, 24281367). |
| Service de Génétique Moléculaire, |
RCV001255733 | SCV001432306 | likely pathogenic | Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability | no assertion criteria provided | clinical testing |