Table 2 HGVS descriptions, SpliceAI, SpliceAI-visual scores, and ACMG classification of the variants analyzed in this study

SCN1A

NM_001165963.4:c.4002 + 2461 T > C p.?

AG = 0.18 (35)

AL = 0

DG = 0.15 (− 28)

DL = 0

Ref: A = 0.64 (35), D = 0.73 (− 28)

Var: A = 0.82 (35), D = 0.87 (− 28)

DS pitfall

pseudo-exonization/Li et al., 2021

Likely pathogenic (PS3, PM2, PP1)

MFGE8

NM_005928.4:c.871-803A > G p.?

AG = 0.15 (144)

AL = 0

DG = 0.16 (43)

DL = 0

Ref: A = 0.68 (144), D = 0.58 (43)

Var: A = 0.84 (144), D = 0.74 (43)

DS pitfall

Yamaguchi et al., 2010

Not Applicable (candidate gene)

SETD5

NM_001080517.3:c.2476 + 198A > C p. ?

AG = 0.05 (− 61)

AL = 0

DG = 0.04 (35)

DL = 0

Ref: A = 0.94 (− 61), D = 0.96 (35)

Var: A = 0.99 (− 61), D = 0.99 (35)

DS pitfall

This study

Pathogenic (PS3, PS2, PM2)

GRN

NM_002087.4:c.-9A > G p.?

AG = 0

AL = 0

DG = 0.19 (272)

DL = 0.48 (1)

Ref: D = 0.94 (1)

Var: D = 0.44 (1)

DS pitfall

This study

Likely pathogenic (PS3, PP5, PM2, PP4)

CASK

NM_001367721.1:c.172 + 1G > A p. ?

AG = 0

AL = 0

DG = 0.71 (− 17)

DL = 0.99 (1)

Ref: D = 0 (1), D = 0.29 (− 17)

Var: D = 0 (1), D = 0.99 (− 17)

Adjusting PVS1

Intronic retention of 18 bp leading to the in-frame insertion of 6 amino acids

r.172_173ins[172 + 1_172 + 18]

p.(Asp58delinsGlyLysArgTrpIleSerAsn)

This study

Uncertain significance (PVS1_M, PM2)

KMT2D

NM_003482.4:c.5189-1G > C p.?

AL = 0.98 (− 1)

DL = 0

AG = 0.95 (− 25)

DG = 0.07 (− 253)

Ref: A = 1 (1), A = 0.04 (− 25)

Var: A = 0.02 (1), A = 0.99 (− 25)

Adjusting PVS1

11 individuals in UK Biobank exomes, prediction of the in-frame deletion of 8 amino acids

Uncertain significance (PVS1_M, PP5, BS2)

NM_003482.4:c.5782 + 1G > A p.?

AL = 0

DL = 1 (1)

AG = 0.01 (− 431)

DG = 0.28 (− 8)

Ref: D = 1 (1), D = 0.71 (− 8)

Var: D = 0 (1), D = 1 (− 8)

Adjusting PVS1

3 heterozygous individuals in gnomAD, prediction of the in-frame insertion of 3 amino acids

Uncertain significance (PVS1_M, PP5, BS2)

TTN

NM_001267550.2:c.31349-1G > C p. ?

AG = 0.51 (− 10)

AL = 0.97 (− 1)

DG = 0 (43)

DL = 0 (1)

Ref: A = 0.97 (− 1), A = 0.02 (− 10), D = 0.99 (− 78)

Var: A = 0 (− 1), A = 0,53 (− 10), D = 0.80 (− 78)

Adjusting PVS1

In-frame rescue acceptor site, leading to the loss of 9 bp

This study

Uncertain significance (PVS1_M, PM2)

SETD5

NM_001080517.3:c.568-31_568dup p.(Asn190Ilefs*20)

AG = 0.07 (0)

AL = 0.01 (− 3574)

DG = 0

DL = 0.01 (135)

Ref: A = 0.99 (31), D = 0.98 (278)

Var: A = 0.99 (31), D = 0.98 (278)

Adjusting PVS1

This study

Benign (PM2, BS3, BS4) Of note, PVS1 has been excluded

EYS

NM_001142800.2:c.2992_2992 + 6delinsTG p.?

Not supported

Ref: A = 0.97 (151), D = 0.99 (6)

Var: A = 0.13 (151), D = 0 (6)

Complex delins

Westin et al. 2021

Likely pathogenic (PS3, PM2, PM3)