Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000085548 | SCV002260774 | likely pathogenic | not provided | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1036 of the ABCA4 protein (p.Glu1036Lys). This variant is present in population databases (rs61750061, gnomAD 0.02%). This missense change has been observed in individual(s) with ABCA4-related conditions (PMID: 10958763, 24938718, 26780318, 29975949, 32845068, 33090715, 33301772). ClinVar contains an entry for this variant (Variation ID: 7886). 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 not expected to disrupt ABCA4 protein function with a negative predictive value of 95%. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003398468 | SCV004122671 | pathogenic | Stargardt disease | 2023-10-10 | criteria provided, single submitter | clinical testing | Variant summary: ABCA4 c.3106G>A (p.Glu1036Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251316 control chromosomes. c.3106G>A has been reported in the literature in multiple individuals affected with Stargardt Disease or cone-rod dystrophy (e.g. Liu_2020, Liu_2021, Sun_2021, Jiang_2016), and some were reported as compound heterozygous with other pathogenic variants. These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 24938718, 32845068, 33090715, 33301772, 33732702, 26780318). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000008337 | SCV000028545 | pathogenic | Severe early-childhood-onset retinal dystrophy | 1998-01-01 | no assertion criteria provided | literature only | |
| Retina International | RCV000085548 | SCV000117685 | not provided | not provided | no assertion provided | not provided |