Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188244 | SCV000241853 | uncertain significance | not provided | 2018-09-07 | criteria provided, single submitter | clinical testing | The Thr441Met missense change has not been published as a mutation, nor as it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Thr441Met in approximately 5,800 individuals of European or African American ancestry, indicating that it not a common benign variant in these populations. Thr441Met is a non-conservative amino acid substitution as a polar Threonine residue is replaced by a non-polar Methionine residue. It alters a position in the second LNS domain of the NRXN1 protein that is highly conserved across species and in related proteins. To our knowledge, missense mutations have not been previously reported near the Thr441Met position. Some in silico models predict that Thr441Met may be damaging to protein structure and/or function, although others suggest that it is likely benign. Therefore, based on the available information, it is unknown whether Thr441Met is a disease-causing mutation or a rare benign variant.The variant is found in INFANT-EPI panel(s). |
Invitae | RCV001055962 | SCV001220377 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2021-12-15 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 206215). This variant is present in population databases (rs796052764, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 441 of the NRXN1 protein (p.Thr441Met). |