Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001380256 | SCV001578252 | pathogenic | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-03-01 | criteria provided, single submitter | clinical testing | This variant disrupts a region of the SCN9A protein in which other variant(s) (p.Glu1773Glyfs*14) have been determined to be pathogenic (PMID: 25253744). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change creates a premature translational stop signal (p.Trp1689*) in the SCN9A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 289 amino acid(s) of the SCN9A protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive congenital indifference to pain (PMID: 17470132). ClinVar contains an entry for this variant (Variation ID: 1068637). For these reasons, this variant has been classified as Pathogenic. |