FLVCR1 was first reported in relation to autosomal recessive FLVCR1-related retinopathy with or without ataxia (also known as posterior column ataxia-retinitis pigmentosa syndrome; PCARP) in 2010 (Rajadhyaksha et al., PMID: 21070897). This condition is characterized by childhood onset retinal dystrophy and progressive sensory ataxia. At least 321 variants (e.g. missense, in-frame indel, nonsense, frameshift, large deletion, complex rearrangement, etc) have been reported in humans (ClinVar database). Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. This curation includes 12 variants (missense, frameshift, nonsense, intronic) from 11 probands from 5 publications (Rajadhyaksha et al, 2010, PMID: 21070897; Ishiura et al, 2011, PMID: 21267618; Castori et al, 2017, PMID: 28766925; Kuehlewein et al, 2019, PMID 30656474; Grudzinska Pechhacker et al, 2020, PMID: 32822874) in addition to segregation data (Rajadhyaksha et al, 2010, PMID: 21070897). More data is available in the literature but the maximum score for genetic evidence (12 points) has been reached. Experimental evidence included qPCR expression data in mice (Rajadhyaksha et al, 2010, PMID: 21070897), functional studies in patient cells, and a homology model of the protein (Grudzinska Pechhacker et al, 2020, PMID: 32822874). In summary, FLVCR1 has a definitive relationship with FLVCR1-related retinopathy with or without ataxia. This classification was approved by the ClinGen Retina GCEP on August 5, 2021.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.