Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000805850 | SCV000945823 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2018-08-20 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs751754721, ExAC 0.001%). This sequence change replaces asparagine with serine at codon 515 of the NRXN1 protein (p.Asn515Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant has not been reported in the literature in individuals with NRXN1-related disease. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. |