ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.772+1040A>T (rs201741449)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188293 SCV000241904 uncertain significance not specified 2017-10-11 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NRXN1 gene. The K260N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The K260N variant is observed in 33/112602 (0.03%) alleles from individuals of European background (Lek et al., 2016). The K260N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved; and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000691824 SCV000819617 uncertain significance Pitt-Hopkins-like syndrome 2 2020-01-08 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 260 of the NRXN1 protein (p.Lys260Asn). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs201741449, ExAC 0.06%). This variant has not been reported in the literature in individuals with NRXN1-related disease. ClinVar contains an entry for this variant (Variation ID: 206261). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 RCV000718550 SCV000849414 uncertain significance History of neurodevelopmental disorder 2017-05-19 criteria provided, single submitter clinical testing Insufficient evidence
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197580 SCV001368359 likely benign Epilepsy 2018-10-10 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this varinat's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3. This variant was detected in heterozygous state.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.