ClinVar Miner

Submissions for variant NM_001384910.1(GUCA1A):c.451C>T (p.Leu151Phe)

dbSNP: rs121434631
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
Blueprint Genetics RCV001075676 SCV001241304 pathogenic Retinal dystrophy 2019-03-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001383741 SCV001582996 pathogenic not provided 2024-12-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 151 of the GUCA1A protein (p.Leu151Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with cone-rod dystrophy (PMID: 15790869, 24875811, 29555955). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 9152). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects GUCA1A function (PMID: 15790869, 23472098). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001383741 SCV001762049 pathogenic not provided 2021-06-17 criteria provided, single submitter clinical testing
GeneDx RCV001383741 SCV001983256 pathogenic not provided 2021-10-15 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (perturbation of photoresponse and impaired guanylate cyclase inhibitition leading to gain of function resulting in persistent stimulation in dark adapted photoreceptors) (Dell'Orco et al., 2014; Sokal et al., 2005); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23428504, 22183351, 20238026, 20213926, 24875811, 19459154, 24778606, 24024198, 15790869, 23472098, 15735604, 31728034, 29555955, 28559085, 24566882)
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV001075676 SCV005070483 pathogenic Retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
OMIM RCV004593960 SCV000056368 pathogenic Cone-rod dystrophy 14 2005-04-01 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.