ClinVar Miner

Submissions for variant NM_023073.3(CPLANE1):c.4517A>G (p.His1506Arg) (rs141911199)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000192922 SCV000246834 uncertain significance not specified 2015-05-29 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000192922 SCV000314191 likely benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726605 SCV000345784 uncertain significance not provided 2016-09-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000315145 SCV000457396 uncertain significance Joubert syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000726605 SCV000531015 uncertain significance not provided 2018-09-25 criteria provided, single submitter clinical testing The H1506R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The H1506R variant is observed in 206/120748 (0.2%) alleles from individuals of European background (Lek et al., 2016). The H1506R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000625259 SCV000744329 likely benign Joubert syndrome 17 2017-03-16 criteria provided, single submitter clinical testing
Invitae RCV000705931 SCV000834953 uncertain significance Orofaciodigital syndrome 6; Joubert syndrome 17 2018-08-07 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 1506 of the C5orf42 protein (p.His1506Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs141911199, ExAC 0.2%). This variant has not been reported in the literature in individuals with C5orf42-related disease. ClinVar contains an entry for this variant (Variation ID: 210553). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.