Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000724087 | SCV000224877 | uncertain significance | not provided | 2014-09-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000724087 | SCV000536386 | uncertain significance | not provided | 2017-01-19 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the NRXN1 gene. The P501L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P501L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P501L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in Human Gene Mutation Database in association with NRXN1-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000549238 | SCV000651809 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 501 of the NRXN1 protein (p.Pro501Leu). This variant is present in population databases (rs530674644, gnomAD 0.006%). 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: 193621). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
Ambry Genetics | RCV002517666 | SCV003693502 | uncertain significance | Inborn genetic diseases | 2022-10-13 | criteria provided, single submitter | clinical testing | The c.1502C>T (p.P501L) alteration is located in exon 10 (coding exon 9) of the NRXN1 gene. This alteration results from a C to T substitution at nucleotide position 1502, causing the proline (P) at amino acid position 501 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |