Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000289750 | SCV000359284 | uncertain significance | Cone-Rod Dystrophy, Recessive | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000342279 | SCV000359285 | uncertain significance | Stargardt Disease, Recessive | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000393464 | SCV000359286 | uncertain significance | Retinitis Pigmentosa, Recessive | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000283357 | SCV000359287 | uncertain significance | Macular degeneration | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
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, |
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. |