Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001041517 | SCV001205138 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 41 of the NRXN1 protein (p.Thr41Met). 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: 839700). 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 disruptive. 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. |
Ambry Genetics | RCV002372772 | SCV002667358 | uncertain significance | Inborn genetic diseases | 2018-12-28 | criteria provided, single submitter | clinical testing | The p.T41M variant (also known as c.122C>T), located in coding exon 1 of the NRXN1 gene, results from a C to T substitution at nucleotide position 122. The threonine at codon 41 is replaced by methionine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |