ClinVar Miner

Submissions for variant NM_001384732.1(CPLANE1):c.3380C>T (p.Ser1127Leu)

gnomAD frequency: 0.00003  dbSNP: rs375009168
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000501748 SCV000593808 likely pathogenic Joubert syndrome 17 2015-08-26 criteria provided, single submitter clinical testing
GeneDx RCV000521353 SCV000618318 likely pathogenic not provided 2019-03-19 criteria provided, single submitter clinical testing Identified in a patient with Joubert syndrome in the published literature (Romani et al., 2015); however, additional information was not provided; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 24178751, 25407461, 31158925)
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000501748 SCV003936837 likely pathogenic Joubert syndrome 17 2023-07-06 criteria provided, single submitter clinical testing
Invitae RCV000521353 SCV004293710 pathogenic not provided 2023-09-15 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1127 of the CPLANE1 protein (p.Ser1127Leu). This variant is present in population databases (rs375009168, gnomAD 0.005%). This missense change has been observed in individual(s) with Oral-facial-digital syndrome (PMID: 24178751, 31158925). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 157515). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CPLANE1 protein function. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000144860 SCV000191880 pathogenic Orofaciodigital syndrome type 6 2014-03-01 no assertion criteria provided literature only

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