Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000475838 | SCV000552208 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 160 of the NRXN1 protein (p.Pro160Leu). This variant is present in population databases (rs371517584, gnomAD 0.04%). 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: 411165). 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 tolerated. 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. |
Gene |
RCV001584165 | SCV001821076 | uncertain significance | not provided | 2023-08-03 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002525595 | SCV003734787 | uncertain significance | Inborn genetic diseases | 2020-11-04 | criteria provided, single submitter | clinical testing | The c.479C>T (p.P160L) alteration is located in exon 2 (coding exon 1) of the NRXN1 gene. This alteration results from a C to T substitution at nucleotide position 479, causing the proline (P) at amino acid position 160 to be replaced by a leucine (L). Based on data from the Genome Aggregation Database (gnomAD) database, the NRXN1 c.479C>T alteration was observed in 0.0043% (12/276370) of total alleles studied, with a frequency of 0.03% (12/35082) in the Latino subpopulation. This amino acid position is well conserved in available vertebrate species. The in silico prediction for the p.P160L alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |