Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001869182 | SCV002183311 | uncertain significance | not provided | 2023-08-17 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 635493). This missense change has been observed in individual(s) with Stargardt disease (PMID: 30060493). This variant is present in population databases (rs377398404, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1566 of the ABCA4 protein (p.Leu1566Phe). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCA4 protein function. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782547 | SCV005395430 | uncertain significance | not specified | 2024-09-18 | criteria provided, single submitter | clinical testing | Variant summary: ABCA4 c.4696C>T (p.Leu1566Phe) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251444 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4696C>T has been reported in the literature in a complex genotype in at least 2 individuals affected with Stargardt disease (example, Nassisi_2018, Khan_2020), including 1 individual who carried a pathogenic variant on the same allele in cis. These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32307445, 30060493). ClinVar contains an entry for this variant (Variation ID: 635493). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000786954 | SCV000925859 | uncertain significance | Cone-rod dystrophy 3 | 2018-10-09 | no assertion criteria provided | clinical testing |