ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.2304G>A (p.Met768Ile)

gnomAD frequency: 0.00003  dbSNP: rs201736678
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000239913 SCV000299170 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 2023-11-20 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 757 of the SCN9A protein (p.Met757Ile). This variant is present in population databases (rs201736678, gnomAD 0.007%). This missense change has been observed in individual(s) with small fiber neuropathy (PMID: 30554136). ClinVar contains an entry for this variant (Variation ID: 254096). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN9A protein function with a negative predictive value of 95%. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001509166 SCV001715727 uncertain significance not provided 2020-07-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002446483 SCV002732053 uncertain significance Inborn genetic diseases 2019-12-12 criteria provided, single submitter clinical testing The p.M757I variant (also known as c.2271G>A), located in coding exon 13 of the SCN9A gene, results from a G to A substitution at nucleotide position 2271. The methionine at codon 757 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.