Description
The c.5726A>G (p.Q1909R) alteration is located in exon 28 (coding exon 27) of the SCN5A gene. This alteration results from a A to G substitution at nucleotide position 5726, causing the glutamine (Q) at amino acid position 1909 to be replaced by an arginine (R). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). One individual with a definite diagnosis of Long QT syndrome was observed to have this variant, and it was not detected in 1300 healthy controls (Kapa, 2009). This variant was also reported in a child with SIDS (Winkel, 2015). This amino acid position is highly conserved in available vertebrate species. While this variant occurs at the interface with Calmodulin, a protein central in regulation of heart rhythm, internal structural analysis indicates this variant may not be sufficiently destabilizing to suggest pathogenicity (Wang, 2012; Gabelli, 2014; Ambry internal data). In vitro functional data suggests that this variant may interfere with channel gating (Winkel, 2015). This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
