ClinVar Miner

Submissions for variant NM_001384732.1(CPLANE1):c.968C>T (p.Thr323Met)

gnomAD frequency: 0.00003  dbSNP: rs373704405
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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 RCV000201580 SCV000256323 pathogenic Joubert syndrome 17 2015-02-23 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000180684 SCV002285719 likely pathogenic not provided 2023-09-25 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 199170). 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. 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. This missense change has been observed in individual(s) with Joubert syndrome (PMID: 26092869). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 323 of the CPLANE1 protein (p.Thr323Met). This variant is present in population databases (rs373704405, gnomAD 0.009%).
Neuberg Centre For Genomic Medicine, NCGM RCV000201580 SCV005042719 uncertain significance Joubert syndrome 17 criteria provided, single submitter clinical testing The missense variant c.968C>Tp.Thr323Met in CPLANE1 gene has been reported in compound heterozygous state in individual affected with Joubert syndrome 17 Bachmann-Gagescu et. al., 2015. The observed variant has been reported with allele frequency of 0.003% in gnomAD exomes database. This variant has been reported to the ClinVar database as Pathogenic/Uncertain Significance. The amino acid change p.Thr323Met in CPLANE1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Thr at position 323 is changed to a Met changing protein sequence and it migalter its composition and physico-chemical properties. Functional studies will be required to confirm the pathogenicity of the variant. For these reasons, this variant has been classified as Uncertain Significance VUS.
Eurofins Ntd Llc (ga) RCV000180684 SCV000233163 uncertain significance not provided 2015-02-14 flagged submission clinical testing

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