ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.2609C>T (p.Pro870Leu) (rs746566873)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408530 SCV000281850 likely pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000490201 SCV000577641 likely pathogenic not provided 2020-07-16 criteria provided, single submitter clinical testing Not observed at a 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: 29925512, 25474345, 28118664)
Blueprint Genetics RCV001074708 SCV001240301 likely pathogenic Retinal dystrophy 2019-04-03 criteria provided, single submitter clinical testing
Invitae RCV000490201 SCV001540159 uncertain significance not provided 2020-03-31 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 870 of the ABCA4 protein (p.Pro870Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs746566873, ExAC 0.002%). This variant has been observed in individual(s) with Stargardt disease (PMID: 25474345, 28118664, 29925512, Invitae). ClinVar contains an entry for this variant (Variation ID: 236093). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Pro870 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been observed in individuals with ABCA4-related conditions (PMID: 25066811, 29925512), which suggests that this may be a clinically significant amino acid residue. 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.

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.