Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188278 | SCV000241889 | uncertain significance | not provided | 2016-05-27 | criteria provided, single submitter | clinical testing | The R896W variant 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 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R896W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other 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, other missense mutations in nearby residues have not been reported in the Human Gene Mutation Database (Stenson et al., 2014). Based on the currently available information, it is unclear whether the R896W variant is a pathogenic mutation or a rare benign variant. |
Invitae | RCV001857625 | SCV002214040 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2022-04-06 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 896 of the NRXN1 protein (p.Arg896Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of NRXN1-related conditions (PMID: 30709877, 32942984). This variant is also known as R856W. ClinVar contains an entry for this variant (Variation ID: 206248). Experimental studies have shown that this missense change affects NRXN1 function (PMID: 32942984). 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. |