Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000688095 | SCV000815694 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1447 of the NRXN1 protein (p.Asn1447Ser). This variant is present in population databases (rs146968018, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 567894). 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 with a negative predictive value of 80%. 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. |
Gene |
RCV001555116 | SCV001776473 | uncertain significance | not provided | 2020-09-25 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002331338 | SCV002632177 | uncertain significance | Inborn genetic diseases | 2018-01-26 | criteria provided, single submitter | clinical testing | The p.N1447S variant (also known as c.4340A>G), located in coding exon 23 of the NRXN1 gene, results from an A to G substitution at nucleotide position 4340. The asparagine at codon 1447 is replaced by serine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |