ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.926C>G (p.Pro309Arg) (rs61748545)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000085874 SCV000321334 likely pathogenic not provided 2018-10-18 criteria provided, single submitter clinical testing The P309R variant in the ABCA4 gene has been reported previously in association with autosomal recessive Stargardt disease when present with another disease-causing variant in the ABCA4 gene (Briggs et al., 2001; Cideciyan et al., 2009; Zernant et al., 2014; Carss et al., 2017). The P309R variant is observed in 39/24,022 (0.1624%) alleles from individuals of African background in large population cohorts and no individuals were reported to be homozygous (Lek et al., 2016). The P309R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret P309R as a likely pathogenic variant.
Blueprint Genetics RCV001075838 SCV001241477 likely pathogenic Retinal dystrophy 2019-08-01 criteria provided, single submitter clinical testing
Invitae RCV000085874 SCV001382437 uncertain significance not provided 2019-11-08 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 309 of the ABCA4 protein (p.Pro309Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is present in population databases (rs61748545, ExAC 0.2%). This variant has been observed in individuals with Stargardt disease (PMID: 25066811, 22247458) and in an individual with macular dystrophy (PMID: 28041643). ClinVar contains an entry for this variant (Variation ID: 99513). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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.
Retina International RCV000085874 SCV000118017 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504769 SCV000599027 likely pathogenic Macular dystrophy 2015-01-01 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.