Table 6 Open in new tab List of gene...

Clinical phenotype

Neuropathic pain grading

Gene

Nucleotide change

Amino acid change

Assigned pathogenicity

Erythromelalgia

Definite

SCN9A

c.2543T>C

p.Ile848Thr

Pathogenic

Erythromelalgia

Definite

SCN9A

c.2543T>C

p.Ile848Thr

Pathogenic

Sensorimotor neuropathy

Probable

SPTLC1

c.399T>G

p.Cys133Trp

Pathogenic

Small fibre neuropathy

Definite

SCN10A

c.4984G>A

p.Gly1662Ser

Likely pathogenic

Small fibre neuropathy

Definite

SCN11A

c.4628G>A

p.Cys1543Tyr

Likely pathogenic

Painful sensory neuropathy

Definite

SPTLC2

c.886A>C

p.Ile296Leu

VUS

Non-freezing cold injury

Definite

SCN9A

c.554G>A

p.Arg185His

VUS

Non-freezing cold injury

Definite

SCN9A

c.554G>A

p.Arg185His

VUS

Non-freezing cold injury

Definite

SCN9A

c.554G>A

p.Arg185His

VUS

Non-freezing cold injury

Definite

SCN9A

c.554G>A

p.Arg185His

VUS

Non-freezing cold injury

Definite

SCN9A

c.554G>A

p.Arg185His

VUS

Non-freezing cold injury

Definite

SCN9A

c.554G>A

p.Arg185His

VUS

Small fibre neuropathy

Definite

SCN9A

c.4612T>C

p.Trp1538Arg

VUS

Small fibre neuropathy

Definite

SCN9A

c.1445A>G

p.Lys482Arg

VUS

Small fibre neuropathy

Probable

SCN9A

c.2215A>G

p.Ile739Val

VUS

Small fibre neuropathy

Definite

SCN9A

c.2215A>G

p.Ile739Val

VUS

Painful sensory neuropathy

Probable

SCN9A

c.2215A>G

p.Ile739Val

VUS

Sensorimotor neuropathy

Definite

SCN9A

c.2215A>G

p.Ile739Val

VUS

Small fibre neuropathy

Definite

SCN9A

c.4982A>G

p.Glu1661Gly

VUS

Traumatic neuropathy

Probable

SCN9A

c.554G>A

p.Arg185His

VUS

Painful Sensory neuropathy

Definite

SCN10A

c.3445G>A

p.Pro1149Met

VUS

Small fibre neuropathy

Definite

SCN10A

c.2428G>T

p.Gly810Trp

VUS

Painful sensory neuropathy

Definite

SCN10A

c.2737G>A

p.Ala913Thr

VUS

Erythromelalgia

Probable

SCN10A

c.968A>G

p.Tyr323Cys

VUS

Small fibre neuropathy

Definite

SCN11A

c.2471A>G

p.Glu824Gly

VUS

Episodic pain

Possible

SCN11A

c.1730C>T

p.Pro577Leu

VUS

Table 6

Open in new tab

List of gene variants that were reported and deemed medically actionable, i.e. variants that result in specific, defined medical recommendations

No	Clinical phenotype	Neuropathic pain grading	Gene	Nucleotide change	Amino acid change	Assigned pathogenicity
1	Erythromelalgia	Definite	SCN9A	c.2543T>C	p.Ile848Thr	Pathogenic
2	Erythromelalgia	Definite	SCN9A	c.2543T>C	p.Ile848Thr	Pathogenic
3	Sensorimotor neuropathy	Probable	SPTLC1	c.399T>G	p.Cys133Trp	Pathogenic
4	Small fibre neuropathy	Definite	SCN10A	c.4984G>A	p.Gly1662Ser	Likely pathogenic
5	Small fibre neuropathy	Definite	SCN11A	c.4628G>A	p.Cys1543Tyr	Likely pathogenic
6	Painful sensory neuropathy	Definite	SPTLC2	c.886A>C	p.Ile296Leu	VUS
7	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
8	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
9	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
10	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
11	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
12	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
13	Small fibre neuropathy	Definite	SCN9A	c.4612T>C	p.Trp1538Arg	VUS
14	Small fibre neuropathy	Definite	SCN9A	c.1445A>G	p.Lys482Arg	VUS
15	Small fibre neuropathy	Probable	SCN9A	c.2215A>G	p.Ile739Val	VUS
16	Small fibre neuropathy	Definite	SCN9A	c.2215A>G	p.Ile739Val	VUS
17	Painful sensory neuropathy	Probable	SCN9A	c.2215A>G	p.Ile739Val	VUS
18	Sensorimotor neuropathy	Definite	SCN9A	c.2215A>G	p.Ile739Val	VUS
19	Small fibre neuropathy	Definite	SCN9A	c.4982A>G	p.Glu1661Gly	VUS
20	Traumatic neuropathy	Probable	SCN9A	c.554G>A	p.Arg185His	VUS
21	Painful Sensory neuropathy	Definite	SCN10A	c.3445G>A	p.Pro1149Met	VUS
22	Small fibre neuropathy	Definite	SCN10A	c.2428G>T	p.Gly810Trp	VUS
23	Painful sensory neuropathy	Definite	SCN10A	c.2737G>A	p.Ala913Thr	VUS
24	Erythromelalgia	Probable	SCN10A	c.968A>G	p.Tyr323Cys	VUS
25	Small fibre neuropathy	Definite	SCN11A	c.2471A>G	p.Glu824Gly	VUS
26	Episodic pain	Possible	SCN11A	c.1730C>T	p.Pro577Leu	VUS

No	Clinical phenotype	Neuropathic pain grading	Gene	Nucleotide change	Amino acid change	Assigned pathogenicity
1	Erythromelalgia	Definite	SCN9A	c.2543T>C	p.Ile848Thr	Pathogenic
2	Erythromelalgia	Definite	SCN9A	c.2543T>C	p.Ile848Thr	Pathogenic
3	Sensorimotor neuropathy	Probable	SPTLC1	c.399T>G	p.Cys133Trp	Pathogenic
4	Small fibre neuropathy	Definite	SCN10A	c.4984G>A	p.Gly1662Ser	Likely pathogenic
5	Small fibre neuropathy	Definite	SCN11A	c.4628G>A	p.Cys1543Tyr	Likely pathogenic
6	Painful sensory neuropathy	Definite	SPTLC2	c.886A>C	p.Ile296Leu	VUS
7	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
8	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
9	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
10	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
11	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
12	Non-freezing cold injury	Definite	SCN9A	c.554G>A	p.Arg185His	VUS
13	Small fibre neuropathy	Definite	SCN9A	c.4612T>C	p.Trp1538Arg	VUS
14	Small fibre neuropathy	Definite	SCN9A	c.1445A>G	p.Lys482Arg	VUS
15	Small fibre neuropathy	Probable	SCN9A	c.2215A>G	p.Ile739Val	VUS
16	Small fibre neuropathy	Definite	SCN9A	c.2215A>G	p.Ile739Val	VUS
17	Painful sensory neuropathy	Probable	SCN9A	c.2215A>G	p.Ile739Val	VUS
18	Sensorimotor neuropathy	Definite	SCN9A	c.2215A>G	p.Ile739Val	VUS
19	Small fibre neuropathy	Definite	SCN9A	c.4982A>G	p.Glu1661Gly	VUS
20	Traumatic neuropathy	Probable	SCN9A	c.554G>A	p.Arg185His	VUS
21	Painful Sensory neuropathy	Definite	SCN10A	c.3445G>A	p.Pro1149Met	VUS
22	Small fibre neuropathy	Definite	SCN10A	c.2428G>T	p.Gly810Trp	VUS
23	Painful sensory neuropathy	Definite	SCN10A	c.2737G>A	p.Ala913Thr	VUS
24	Erythromelalgia	Probable	SCN10A	c.968A>G	p.Tyr323Cys	VUS
25	Small fibre neuropathy	Definite	SCN11A	c.2471A>G	p.Glu824Gly	VUS
26	Episodic pain	Possible	SCN11A	c.1730C>T	p.Pro577Leu	VUS

Clinically relevant, medically actionable, variants were reported to the referring clinician. All participants were heterozygous for the relevant variants. All variants were predicted by Ensembl Variant Effect Predictor as missense variants (see Supplementary Table 1 for details of allele frequencies of variants in databases, in silico analysis and a list of publications where variants effects on ion channels were studied).

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