Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000086234 | SCV000321388 | likely pathogenic | not provided | 2024-10-22 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate abnormal gene splicing (PMID: 26650897); In silico analysis supports that this missense variant has a deleterious effect on splicing; In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 15469903, 15180275, 22412862, 15347646, 22347407, 20301475, 15081406, 24596939, 25799540, 12374762, 16052170, 20702822, 10873396, 26650897, 35456422, 31964843, 38219857) |
| Labcorp Genetics |
RCV000055941 | SCV001219632 | pathogenic | Leber congenital amaurosis 4 | 2025-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 262 of the AIPL1 protein (p.Gly262Ser). RNA analysis indicates that this missense change induces altered splicing and likely disrupts the C-terminus of the protein. This variant is present in population databases (rs142326926, gnomAD 0.006%). This missense change has been observed in individuals with Leber congenital amaurosis (PMID: 10873396, 15249368, 20702822). ClinVar contains an entry for this variant (Variation ID: 65711). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AIPL1 protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on AIPL1 function (PMID: 15347646, 22347407, 25799540, 27268253, 28973376). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in partial skipping of exon 5 and introduces a new termination codon (PMID: 26650897). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000055941 | SCV000086965 | not provided | Leber congenital amaurosis 4 | no assertion provided | literature only | ||
| Retina International | RCV000086234 | SCV000118380 | not provided | not provided | no assertion provided | not provided | ||
| Prevention |
RCV004732645 | SCV005361230 | pathogenic | AIPL1-related disorder | 2024-08-29 | no assertion criteria provided | clinical testing | The AIPL1 c.784G>A variant is predicted to result in the amino acid substitution p.Gly262Ser. This variant has been reported in the compound heterozygous state in individuals with autosomal recessive Leber congenital amaurosis (Sohocki et al. 2000. PubMed ID: 10873396; Table S1, Zhu et al. 2022. PubMed ID: 35456422; Table S1, Lin et al. 2024. PubMed ID: 38219857). This variant affects the last nucleotide of exon 5 and a functional study using a minigene assay has shown that this variant alters splicing (Bellingham et al. 2015. PubMed ID: 26650897). This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic. |