Submissions for variant NM_001384732.1(CPLANE1):c.3599C>A (p.Ala1200Glu)

dbSNP: rs141153181

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001935562	SCV002197364	pathogenic	not provided	2021-01-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ala1200 amino acid residue in CPLANE1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24091540, 25407461, 27081551, 29605658). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant has been observed in individual(s) with CPLANE1-related conditions (PMID: 29605658). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with glutamic acid at codon 1200 of the CPLANE1 protein (p.Ala1200Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid.
Fulgent Genetics, Fulgent Genetics	RCV002503596	SCV002783660	likely pathogenic	Orofaciodigital syndrome type 6; Joubert syndrome 17	2022-04-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001935562	SCV004023866	likely pathogenic	not provided	2023-09-26	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29605658, 26092869, 24091540, 25407461)