Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188259 | SCV000241869 | uncertain significance | not provided | 2012-08-31 | criteria provided, single submitter | clinical testing | The Phe70Leu 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 Phe70Leu 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 Phenylalanine and Leucine are uncharged, non-polar amino acids, and it alters a position in the protein that is not conserved. Additionally, multiple in silico algorithms predict it is likely benign. Therefore, the clinical and molecular information available at this time suggests that this variant is likely non-pathogenic; however, the possibility that it is a disease-associated mutation cannot be completely excluded. The variant is found in EPILEPSY panel(s). |
Invitae | RCV001852478 | SCV002124878 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2022-08-12 | 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: 206230). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 70 of the NRXN1 protein (p.Phe70Leu). |