Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188274 | SCV000241884 | uncertain significance | not provided | 2012-09-26 | criteria provided, single submitter | clinical testing | The Asn190Lys missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Asn190Lys in approximately 6,200 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as an uncharged Asparagine residue is replaced by a positively charged Lysine residue. Asn190Lys alters a position that is not conserved in the neurexin1 protein but is highly conserved in related proteins, and several in silico algorithms predict Asn190Lys may be damaging to protein structure/function. Therefore, based on the currently available information, it is unclear whether Asn190Lys is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Invitae | RCV000818582 | SCV000959202 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2022-03-12 | 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 206244). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. This variant is present in population databases (rs564945882, gnomAD 0.02%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 190 of the NRXN1 protein (p.Asn190Lys). |