Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001350170 | SCV001544552 | likely pathogenic | not provided | 2022-11-29 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1083 of the ABCA4 protein (p.Val1083Glu). This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1045711). This missense change has been observed in individual(s) with clinical features of Stargardt disease (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004699327 | SCV005204359 | uncertain significance | not specified | 2024-06-12 | criteria provided, single submitter | clinical testing | Variant summary: ABCA4 c.3248T>A (p.Val1083Glu) results in a non-conservative amino acid change located in the ATP-binding cassette, ABC transporter-type domain profile (IPR003439) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251474 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3248T>A in individuals affected with Retinitis Pigmentosa and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1045711). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV005023077 | SCV005657424 | likely pathogenic | Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 | 2024-06-17 | criteria provided, single submitter | clinical testing |