ClinVar Miner

Submissions for variant NM_019892.6(INPP5E):c.1132C>T (p.Arg378Cys) (rs121918130)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735369 SCV000854522 pathogenic Talipes equinovarus; Skeletal dysplasia; Micrognathia; Hemivertebrae; Preaxial foot polydactyly; Respiratory failure; Short femur; Vertebral segmentation defect; Pseudoarthrosis; Chronic lung disease; Interstitial pulmonary abnormality; Coat hanger sign of ribs; Vertebral hypoplasia; Absent epiphyses; Cleft palate; Patent ductus arteriosus criteria provided, single submitter clinical testing
Invitae RCV000636941 SCV000758388 likely pathogenic Joubert syndrome 2017-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 378 of the INPP5E protein (p.Arg378Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs121918130, ExAC 0.03%). This variant has been reported to be homozygous in individuals affected with Joubert syndrome (PMID: 19668216). ClinVar contains an entry for this variant (Variation ID: 400). An experimental study has shown that this missense change disrupts INPP5E phosphatase activity in vitro and in cell culture (PMID: 19668216). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000022405 SCV000043090 pathogenic Joubert syndrome 1 2009-09-01 no assertion criteria provided literature only

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