Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001236846 | SCV001409584 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2023-10-25 | criteria provided, single submitter | clinical testing | This sequence change affects codon 426 of the NRXN1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NRXN1 protein. This variant also falls at the last nucleotide of exon 8, which is part of the consensus splice site for this exon. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 962909). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |
Prevention |
RCV003973156 | SCV004793124 | uncertain significance | NRXN1-related condition | 2023-12-28 | criteria provided, single submitter | clinical testing | The NRXN1 c.1278G>A variant is not predicted to result in an amino acid change (p.=). However, such splice predictions are not equivalent to functional evidence. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0085% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |