ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.4945C>T (p.Pro1649Ser)

gnomAD frequency: 0.00001  dbSNP: rs886046563
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000289750 SCV000359284 uncertain significance Cone-Rod Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000342279 SCV000359285 uncertain significance Stargardt Disease, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000393464 SCV000359286 uncertain significance Retinitis Pigmentosa, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000283357 SCV000359287 uncertain significance Macular degeneration 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001101749 SCV001258386 uncertain significance ABCA4-Related Disorders 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001812786 SCV001472423 uncertain significance not provided 2019-11-28 criteria provided, single submitter clinical testing The ABCA4 p.Pro1649Ser variant (rs886046563), to our knowledge, has not been reported in the medical literature; however, this variant is listed in the ClinVar database (Variation ID: 298231). This variant is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The proline at codon 1649 is highly conserved (Alamut v.2.11) but computational analyses (SIFT: Tolerated, PolyPhen-2: Possibly damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Pro1649Ser variant is uncertain at this time.
Invitae RCV001812786 SCV002158906 uncertain significance not provided 2021-11-18 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1649 of the ABCA4 protein (p.Pro1649Ser). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ABCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 298231). 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. 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.