Table 3.
Potentially pathogenic variants of ion channel genes identified in patients with painless-diabetic neuropathy (n = 304).
| Gene | c. Position & | p. Position | Number of Patients | Classification Based Richards et al. [22] | Location | MAF GnomAD (%) | Ref. |
|---|---|---|---|---|---|---|---|
| ANO1 | c.1892G>A | p.(Arg631Gln) | 1 | VUS | Linker between transmembrane domain V and VI | 0.012 | - |
| KCNK18 | c.414_415del | p.(Phe139Trpfs*25) | 1 | VUS | Exon 3, the new reading frame ends in a STOP codon at position 25 | 0.043 | [19,20,21,23] |
| c.361dup | p.(Tyr121Leufs*44) | 2 | VUS | Exon 3, the new reading frame ends in a STOP codon at position 44 | 0.024 | [19] | |
| KCNQ3 | c.1226C>G | p.(Pro409Arg) | 1 | VUS | C-terminus | 0.067 | - |
| TRPA1 | c.352C>G | p.(Leu118Val) | 1 | VUS | Ankyrin repeat II-containing domain | 0.047 | - |
| c.1980C>A | p.(Phe660Leu) | 1 | VUS | Cytoplasmic domain between ANK repeats and transmembrane domain I | 0.01 | - | |
| TRPM8 | c.2956G>A | p.(Val986Ile) | 1 | VUS | C-terminus | 0.002 | - |
| TRPV1 | c.1450G>C | p.(Gly484Arg) | 1 | VUS | Transmembrane domain II | 0 | - |
| c.1781C>T | p.(Ala594Val) | 1 | VUS | Transmembrane domain V | 0.042 | - | |
| c.1790C>T | p.(Thr597Met) | 1 | VUS | Transmembrane domain V | 0.0021 | - | |
| TRPV4 | c.711A>G | p.? # | 1 | VUS | Ankyrin repeat I-containing domain | 0.0008 | - |
| c.958C>T | p.(Arg320*) | 1 | VUS | N-terminus | 0.0039 | - | |
| c.1039G>T | p.(Asp347Tyr) | 1 | VUS | N-terminus | 0.018 | - |
c. position, location cDNA; p. position, location in protein; MAF gnomAD, minor allele frequency the Genome Aggregation Database; n/a, not applicable; VUS, variants with uncertain clinical significance. & Variants detected were annotated according to the guidelines of the Human Genome Variation Society using reference sequence GRCh37 and transcript numbers, NM_018043.5 (ANO1); NM_181840.1 (KCNK18), NM_004519.3 (KCNQ3), NM_007332.2 (TRPA1); NM_024080.4 (TRPM8); NM_080706.3 (TRPV1); NM_021625.4 (TRPV4); # predicted alternative splice sites would lead to a premature stop codon.