Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001221679 | SCV001393739 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 95 of the NRXN1 protein (p.Ile95Val). This variant is present in population databases (rs778259562, gnomAD 0.02%). 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: 950057). 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 | RCV002436857 | SCV002750481 | uncertain significance | Inborn genetic diseases | 2018-12-04 | criteria provided, single submitter | clinical testing | The p.I95V variant (also known as c.283A>G), located in coding exon 1 of the NRXN1 gene, results from an A to G substitution at nucleotide position 283. The isoleucine at codon 95 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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. |