Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001378124 | SCV001575624 | likely pathogenic | Hereditary insensitivity to pain with anhidrosis | 2023-07-13 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 11 of the NTRK1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NTRK1 are known to be pathogenic (PMID: 10982191). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NTRK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1066982). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Gene |
RCV001587384 | SCV001825331 | likely pathogenic | not provided | 2020-06-01 | criteria provided, single submitter | clinical testing | Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
| Genome- |
RCV001378124 | SCV004048732 | likely benign | Hereditary insensitivity to pain with anhidrosis | 2023-04-11 | criteria provided, single submitter | clinical testing |