Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001840988 | SCV001353954 | uncertain significance | Cardiac arrhythmia | 2023-02-22 | criteria provided, single submitter | clinical testing | This variant is located in the 3' untranslated region of the SCN5A gene, 1 nucleotide downstream from the stop codon. To our knowledge, functional studies have not been reported for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 15/209454 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001420833 | SCV001623225 | benign | not specified | 2021-05-03 | criteria provided, single submitter | clinical testing | Variant summary: SCN5A c.*1G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 7.3e-05 in 178056 control chromosomes, predominantly at a frequency of 0.00076 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4.6-fold the estimated maximal expected allele frequency for a pathogenic variant in SCN5A causing Brugada Syndrome With Sudden Cardiac Death phenotype (0.00017), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.*1G>A in individuals affected with Brugada Syndrome With Sudden Cardiac Death and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign. |
| Gene |
RCV001712877 | SCV001944468 | likely benign | not provided | 2019-12-26 | criteria provided, single submitter | clinical testing |