ClinVar Miner

Submissions for variant NM_014336.5(AIPL1):c.364G>C (p.Gly122Arg)

gnomAD frequency: 0.00001  dbSNP: rs201883601
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
CeGaT Center for Human Genetics Tuebingen RCV001090635 SCV001246293 pathogenic not provided 2017-10-01 criteria provided, single submitter clinical testing
Invitae RCV001172396 SCV001512042 pathogenic Leber congenital amaurosis 4 2021-09-24 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001172396 SCV001573602 likely pathogenic Leber congenital amaurosis 4 2021-04-08 criteria provided, single submitter research The AIPL1 c.364G>C variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PS3. Based on this evidence we have classified this variant as Likely Pathogenic.
3billion RCV001172396 SCV002058908 likely pathogenic Leber congenital amaurosis 4 2022-01-03 criteria provided, single submitter clinical testing The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 20702822, 21474771, PM3_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.85, PP3_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222668 SCV002500710 likely pathogenic Leber congenital amaurosis 2022-03-28 criteria provided, single submitter clinical testing Variant summary: AIPL1 c.364G>C (p.Gly122Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250732 control chromosomes (gnomAD). c.364G>C has been reported in the literature in individuals affected with Retinal Degeneration (Jacobson_2011, Weisschuh_2020, Sacristan-Reviriego_2020). In addition, a different variant (c.364G>A) with the same coding effect (G122R) was also found in individuals affected with Retinal Degeneration and Leber congenital amaurosis 4, including one homozygote (Testa_2011, Sacristan-Reviriego_2020). These data indicate that the variant is likely to be associated with disease. At least one functional study reports experimental evidence evaluating an impact on protein function and showed no damaging effect of this variant (Sacristan-Reviriego_2020). Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic (n=1), likely pathogenic (n=2) and uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Laboratory of Genetics in Ophthalmology,Institut Imagine RCV001172396 SCV001335457 pathogenic Leber congenital amaurosis 4 no assertion criteria provided research

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.