Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188306 | SCV000241917 | uncertain significance | not specified | 2014-10-06 | criteria provided, single submitter | clinical testing | This variant p.Gly1453Ser alters both the alpha and beta transcripts of the NRXN1 protein. In the shorter beta-neurexin transcript (NM_128735.2), the variant is denoted p.G348S and has been published using alternative nomeclature (G378S) in a patient with autism, intellectual disability and compulsive personality disorder and his mother who had an unspecified mental disorder (Camacho-Garcia et al., 2012). In the primary transcript (NM_001135659.1) the variant is denoted p.G1453S. Regardless of the transcript, this variant is a non-conservative amino acid substitution that alters a position that is conserved in mammals. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s). |
Invitae | RCV000534805 | SCV000651831 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1453 of the NRXN1 protein (p.Gly1453Ser). This variant is present in population databases (rs200604893, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of NRXN1-related conditions (PMID: 22504536, 36703223). This variant is also known as c.1132G>A (p.Gly378Ser). ClinVar contains an entry for this variant (Variation ID: 206273). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NRXN1 protein function with a negative predictive value of 80%. 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. |
Al Jalila Children's Genomics Center, |
RCV002478658 | SCV002775009 | uncertain significance | not provided | 2022-12-17 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002478659 | SCV002778836 | uncertain significance | Pitt-Hopkins-like syndrome 2; Chromosome 2p16.3 deletion syndrome | 2021-11-16 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000534805 | SCV003814154 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2019-05-29 | criteria provided, single submitter | clinical testing |