Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188304 | SCV000241915 | uncertain significance | not specified | 2012-08-23 | criteria provided, single submitter | clinical testing | The Gly507Val missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Gly507Val in approximately 6,000 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is conservative, as both Glycine and Valine are uncharged, non-polar amino acids. However, Gly507Val alters a highly conserved position in the linker region between the LNS2 and LNS3 domains of the protein, and multiple in silico algorithms predict it may be damaging to protein structure/function. Therefore, based on the currently available information, it is unclear whether Gly507Val is a disease-causing mutation or a rare benign variant. The variant is found in CHILD-EPI panel(s). |
Invitae | RCV001852479 | SCV002109025 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2022-09-30 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 206271). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 507 of the NRXN1 protein (p.Gly507Val). |