ClinVar Miner

Submissions for variant NM_000087.3(CNGA1):c.959C>T (rs62625014)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000778730 SCV000915088 likely pathogenic Retinitis pigmentosa 2018-08-29 criteria provided, single submitter clinical testing The CNGA1 c.959C>T (p.Ser320Phe) missense variant, also referred to as c.1166C>T (p.Ser389Phe) and p.Ser316Phe, was found in a compound heterozygous state in six probands, including two sibling pairs, with autosomal recessive retinintis pigmentosa (Dryja et al. 1995; Eisenberger et al. 2013; Comander et al. 2017). Control data is unavailable for this variant, which is reported at a frequency of 0.001914 in the European (non-Finnish) population of the Genome Aggregation Database. Dryja et al. (1995) investigated channel function and found the p.Ser389Phe variant was similar to wild type for channel current and open times of the channel, however, the location was found to be intracellular, whereas wild type CNGA1 protein was located at the cell membrane. Based on the evidence, this variant is classified as likely pathogenic for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000778730 SCV000966829 likely pathogenic Retinitis pigmentosa 2018-09-11 criteria provided, single submitter clinical testing The p.Ser320Phe variant in CNGA1 (also described as p.Ser316Phe and p.Ser389Phe in the literature) has been reported in compound heterozygous state in 4 individ uals with autosomal recessive retinitis pigmentosa (RP), and segregated with dis ease in 2 affected relatives from 2 families (Dryja 1995, Eisenberger 2013, Coma nder 2017). In vitro functional studies provide some evidence that the p.Ser320P he variant may impact protein function (Dryja 1995). This variant has been repor ted in ClinVar (Variation ID: 424770) and has been identified in 0.19% (242/1264 08) Of European chromosomes by the Genome Aggregation Database (gnomAD, http://g nomad.broadinstitute.org; dbSNP rs62625014). Please note that this frequency is low enough to be consistent with the frequency of RP in the general population. In summary, although additional studies are required to fully establish its clin ical significance, the p.Ser320Phe variant is likely pathogenic for RP in an aut osomal recessive manner. ACMG/AMP Criteria applied: PM3_Strong; PP1; PS3_Support ing.
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000778730 SCV000926828 likely pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787817 SCV000926829 likely pathogenic Macular dystrophy 2018-04-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787818 SCV000926830 likely pathogenic Cone-rod dystrophy 2018-04-01 no assertion criteria provided research
OMIM RCV000018440 SCV000038722 pathogenic Retinitis pigmentosa 49 1995-10-24 no assertion criteria provided literature only

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.