ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1895C>T (p.Thr632Met)

gnomAD frequency: 0.00001  dbSNP: rs199473134
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001842302 SCV002051981 uncertain significance Cardiac arrhythmia 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 632 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has shown that the mutant channel has no significantly different sodium current densities compared to the control channel (PMID: 24573164). This variant has been reported in two individuals with suspected Brugada syndrome (PMID: 20129283). This variant has been identified in 3/244512 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV003430657 SCV002160722 uncertain significance not provided 2023-10-16 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 632 of the SCN5A protein (p.Thr632Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of Brugada syndrome (PMID: 20129283, 25904541). ClinVar contains an entry for this variant (Variation ID: 67695). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change does not substantially affect SCN5A function (PMID: 24573164). 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.
Fulgent Genetics, Fulgent Genetics RCV002477196 SCV002793240 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2021-11-01 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003430657 SCV004154190 uncertain significance not provided 2023-08-01 criteria provided, single submitter clinical testing SCN5A: PM2
All of Us Research Program, National Institutes of Health RCV001842302 SCV004832298 uncertain significance Cardiac arrhythmia 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 632 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has shown that the mutant channel has no significantly different sodium current densities compared to the control channel (PMID: 24573164). This variant has been reported in two individuals with suspected Brugada syndrome (PMID: 20129283). This variant has been identified in 3/244512 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004019040 SCV004943821 uncertain significance Cardiovascular phenotype 2020-07-21 criteria provided, single submitter clinical testing The c.1895C>T (p.T632M) alteration is located in exon 13 (coding exon 12) of the SCN5A gene. This alteration results from a C to T substitution at nucleotide position 1895, causing the threonine (T) at amino acid position 632 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000058459 SCV000089979 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:20129283). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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.