Submissions for variant NM_001384732.1(CPLANE1):c.9097C>T (p.Gln3033Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003331844	SCV004037721	pathogenic	Joubert syndrome and related disorders	2023-08-29	criteria provided, single submitter	clinical testing	Variant summary: CPLANE1 c.8935C>T (p.Gln2979X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251476 control chromosomes (gnomAD). c.8935C>T has been reported in the literature in at least one biallelic individual with a phenotype consistent with Joubert Syndrome And Related Disorders (Fitzgerald_2015). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 25533962). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003561305	SCV004284366	pathogenic	not provided	2023-02-16	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with CPLANE1-related conditions (PMID: 25533962). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln2979*) in the CPLANE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPLANE1 are known to be pathogenic (PMID: 24178751, 26092869).