ClinVar Miner

Submissions for variant NM_023073.3(CPLANE1):c.3599C>T (p.Ala1200Val) (rs141153181)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program,University of Washington RCV000201619 SCV000256326 pathogenic Joubert syndrome 17 2015-02-23 criteria provided, single submitter research
GeneDx RCV000255261 SCV000322078 pathogenic not provided 2017-07-03 criteria provided, single submitter clinical testing The A1200V pathogenic variant in the C5orf42 gene has been reported previously in the homozygous or compound heterozygous state in multiple individuals with Joubert syndrome and oral-facial-digital syndrome type V1 (Ohba et al., 2013; Bachmann-Gagescu et al., 2015; Romani et al., 2015). The A1200V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This is a conservative substitution that occurs at a position that is conserved through mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A1200V as a pathogenic variant.
SIB Swiss Institute of Bioinformatics RCV000677320 SCV000803507 uncertain significance Orofaciodigital syndrome type 6 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Uncertain Significance - Insufficient Evidence, for Joubert syndrome with orofaciodigital defect (orofaciodigital syndrome 6), in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product.
Invitae RCV000255261 SCV001379999 pathogenic not provided 2019-08-01 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1200 of the CPLANE1 protein (p.Ala1200Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs141153181, ExAC 0.006%). This variant has been observed in individuals affected with ciliopathy disorders (PMID: 24091540, 25407461, 27081551, 29605658). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This gene is also known as C5orf42 in the literature. ClinVar contains an entry for this variant (Variation ID: 217591). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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