Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000766526 | SCV000241898 | uncertain significance | not provided | 2018-07-17 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the NRXN1 gene. The G213R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G213R variant is observed in 17/107626 (0.02%) alleles from individuals of European background (Lek et al., 2016). The G213R 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. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Genetic Services Laboratory, |
RCV000188287 | SCV000596075 | uncertain significance | not specified | 2016-01-29 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000813276 | SCV000953631 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 213 of the NRXN1 protein (p.Gly213Arg). This variant is present in population databases (rs199561088, 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: 206256). 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. |