Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV001263254 | SCV001441291 | likely pathogenic | Seizure; Intellectual disability | 2020-01-08 | criteria provided, single submitter | clinical testing | The c.1279G>T (p.Gly427Cys) variant identified in the NTRK2 gene substitutes a well conserved Glycine for Cysteine at amino acid 427/839 (coding exon 13/21). This variant is absent from gnomAD suggesting it is not a common benign variant in the populations represented in this database. In silico algorithms do not agree on the effect of this variant, as it is predicted both Neutral (Provean; score: -1.75) and Damaging (SIFT; score: 0.023) to the function of the canonical transcript. The p.Gly427 residue is outside of a mapped domain, however itis 7 amino acids upstream of the recurrent pathogenic p.Tyr434Cys variant identified in several individuals affected with epileptic encephalopathy [PMID: 29100083]. This variant was identified de novo in an indiviudal submitted for clinical WGS. The c.1279G>T (p.Gly427Cys) variant identified in the NTRK2 gene is reported here as Likely Pathogenic. |