Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001050414 | SCV001214520 | pathogenic | not provided | 2024-10-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 104 of the NR2E3 protein (p.Arg104Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with autosomal recessive enhanced S-cone syndrome (ESCS) (PMID: 15459973, 18436841, 19898638, 25079116). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 846973). 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) indicates that this missense variant is expected to disrupt NR2E3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NR2E3 function (PMID: 19823680, 19898638). This variant disrupts the p.Arg104 amino acid residue in NR2E3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16225923, 19898638, 23374571, 25079116, 27522502). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001832466 | SCV004191585 | pathogenic | Enhanced S-cone syndrome | 2024-03-21 | criteria provided, single submitter | clinical testing | |
| Sing |
RCV001832466 | SCV005881545 | likely pathogenic | Enhanced S-cone syndrome | 2025-02-05 | criteria provided, single submitter | clinical testing | Variant is located in a mutational hotspot where >50% of classified variants are pathogenic (PM1). Allele frequency in gnomAD exomes and genomes are < 0.000001, and homozygous allele count are less than 0 (PM2). Other variant at this amino acid residue has been classified as pathogenic/likely pathogenic (PM5, p.Arg104Gln). Experimental studies have shown that this missense change affects NR2E3 function (PS3, PMID: 19823680;19898638) |
| Natera, |
RCV001832466 | SCV002085597 | pathogenic | Enhanced S-cone syndrome | 2020-08-25 | no assertion criteria provided | clinical testing |