Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000221544 | SCV000279949 | uncertain significance | not provided | 2017-03-17 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the NTRK1 gene. The R548Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R548Q variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R548Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in Human Gene Mutation Database in association with NTRK1-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Mendelics | RCV000708820 | SCV000837806 | uncertain significance | Familial medullary thyroid carcinoma | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001276831 | SCV002221207 | likely benign | Hereditary insensitivity to pain with anhidrosis | 2024-01-26 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002399797 | SCV002709383 | uncertain significance | Inborn genetic diseases | 2022-06-10 | criteria provided, single submitter | clinical testing | The p.R548Q variant (also known as c.1643G>A), located in coding exon 13 of the NTRK1 gene, results from a G to A substitution at nucleotide position 1643. The arginine at codon 548 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV001276831 | SCV001463403 | uncertain significance | Hereditary insensitivity to pain with anhidrosis | 2020-04-17 | no assertion criteria provided | clinical testing |