Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000798588 | SCV000938211 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2024-03-30 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 278 of the NRXN1 protein (p.Lys278Asn). This variant is present in population databases (rs200332062, gnomAD 0.002%). 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: 206262). 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 tolerated. 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 | RCV002433849 | SCV002677232 | uncertain significance | Inborn genetic diseases | 2017-10-27 | criteria provided, single submitter | clinical testing | The p.K278N variant (also known as c.834A>C), located in coding exon 2 of the NRXN1 gene, results from an A to C substitution at nucleotide position 834. The lysine at codon 278 is replaced by asparagine, an amino acid with similar properties. This amino acid position is not well conserved in available 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. |