Table 2.

Significant variants identified in long survivors with motor neuron disease (MND)

Gene	Genomic position (GRCh37)	HGVS coding transcript/variant DNA change	Amino acid change	Variant type	Number cases	Number controls	ACMG-AMP/ACGS Evidence
FIG4	6:110113822A > T	NM_014845.5:c.2414A > T	p.(Asn805Ile)	Missense	1	1	PS4, PM2
HNRNPA2B1	7:26240202G > A	NM_031243.2:c.-5C > T	5’ UTR	5’ UTR Variant	1	0	PS4, PM2
SETX	9:135211747C > G	NM_015046.5:c.654G > C	p.(Lys218Asn)	Missense	1	3	PS4, PM2
SOD1	21:33039672 T > C	NM_000454.4:c.341 T > C	p.(Ile114Thr)	Missense	4*	0	PS4, PM2, PP1 Moderate, PP3
SOD1	21:33036142G > A	NM_000454.4:c.112G > A	p.(Gly38Arg)	Missense	1	0	PS4, PM2, PP3
SPAST	2:32366960 T > -	NM_014946.3:c.1494-3delT	Intronic	Intronic splice region	2	0	PS4, PM2, PP3
SQSTM1	5:179260112GAG > -	NM_003900.4:c.835_837delGAG	p.(Glu280del)	Inframe deletion	1	0	PS4, PM2, PP3
SQSTM1	5:179263547C > T	NM_003900.4:c.1277C > T	p.(Ala426Val)	Missense	1	2	PS4, PM2
TAF15	17:34171667A > G	NM_139215.2:c.1364A > G	p.(Tyr455Cys)	Missense	1	0	PS4, PM2, PP3
VAPB	20:56964578G > A	NM_004738.4:c.58 + 5G > A	Intronic	Intronic splice region	1	0	PS4, PM2, PP3

Classification of pathogenicity based on use of American College of Medical Genetics and Association for Molecular Pathology (ACMG-AMP) and Association for Clinical Genomic Science (ACGS) UK 2020 guidelines. All variants detected in heterozygous state. Genomic controls comprised ancestry-matched individuals from the Lothian Birth Cohorts (n = 1385). Variants were considered significantly more prevalent in cases versus controls if odds ratio > 5.0 and confidence intervals did not cross 1.0 (ACMG-AMP criteria PS4). Additionally, gnomAD was used as a population control data set (ACMG criteria PM2). Co-segregation was quantified using methods described by Jarvik et al. (PP1). In silico predictions were evaluated using VarSeq Golden Helix annotations (PP3)

UTR untranslated region

*Indicates that 2 of the cases are related