Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000188242 | SCV000241851 | uncertain significance | not provided | 2013-08-29 | criteria provided, single submitter | clinical testing | The Arg1465Gln missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution of a positively charged Arginine residue with an uncharged Glutamine residue at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations have not been reported in this region of the protein. Therefore, based on the currently available information, it is unclear whether Arg1465Gln is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
| Ambry Genetics | RCV002327013 | SCV002629874 | uncertain significance | Inborn genetic diseases | 2018-04-24 | criteria provided, single submitter | clinical testing | The p.R1465Q variant (also known as c.4394G>A), located in coding exon 23 of the NRXN1 gene, results from a G to A substitution at nucleotide position 4394. The arginine at codon 1465 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003619657 | SCV004529946 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2022-11-30 | criteria provided, single submitter | clinical testing | 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. 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 NRXN1 protein function. ClinVar contains an entry for this variant (Variation ID: 206213). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. This variant is present in population databases (rs201559515, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1465 of the NRXN1 protein (p.Arg1465Gln). |