Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001209450 | SCV001380883 | uncertain significance | Autosomal recessive axonal neuropathy with neuromyotonia | 2019-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 37 of the HINT1 protein (p.Arg37Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HINT1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg37 amino acid residue in HINT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22961002, 25342199, 26182879, 27549087). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |