ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.4304T>C (p.Met1435Thr)

gnomAD frequency: 0.00002  dbSNP: rs759286277
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000804642 SCV000944559 uncertain significance Brugada syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 1435 of the SCN10A protein (p.Met1435Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with SCN10A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV004028184 SCV003997326 uncertain significance Cardiovascular phenotype 2023-04-04 criteria provided, single submitter clinical testing The c.4304T>C (p.M1435T) alteration is located in exon 25 (coding exon 25) of the SCN10A gene. This alteration results from a T to C substitution at nucleotide position 4304, causing the methionine (M) at amino acid position 1435 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, 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.