Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001370056 | SCV001566517 | uncertain significance | Hereditary insensitivity to pain with anhidrosis | 2020-10-19 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NTRK1 protein function. This variant has not been reported in the literature in individuals with NTRK1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with glutamic acid at codon 630 of the NTRK1 protein (p.Ala630Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. |