ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.4733G>A (p.Trp1578Ter) (rs200070962)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000604892 SCV000711767 likely pathogenic Indifference to pain, congenital, autosomal recessive 2018-01-31 criteria provided, single submitter clinical testing The p.Trp1567X variant in SCN9A has not been previously reported in individuals with congenital insensitivity to pain and was absent from large population studi es. This nonsense variant leads to a premature termination codon at position 156 7, which is predicted to lead to a truncated or absent protein. Loss of function of the SCN9A gene is associated with congenital insensitivity to pain. In summa ry, although additional studies are required to fully establish its clinical sig nificance, this variant is likely pathogenic for congenital insensitivity to pai n in an autosomal recessive manner.
Invitae RCV000802734 SCV000942577 pathogenic Hereditary sensory and autonomic neuropathy type IIA; Generalized epilepsy with febrile seizures plus, type 7 2018-12-07 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SCN9A gene (p.Trp1567*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 411 amino acids of the SCN9A protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN9A-related disease. ClinVar contains an entry for this variant (Variation ID: 504889). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the C-terminus of the SCN9A protein. Other variant(s) that disrupt this region (p.Glu1773Glyfs*14) have been determined to be pathogenic (PMID: 25253744, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.