Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188260 | SCV000241870 | uncertain significance | not provided | 2020-12-07 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV001060695 | SCV001225399 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2022-11-08 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 206231). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. This variant is present in population databases (rs201031680, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 73 of the NRXN1 protein (p.Glu73Asp). |