Table 1

Novel pathogenic variants and phenotypes of individuals diagnosed through exome sequencing

Patient
ID
Gene(Chr:position)c.DNA change p.protein changeCoding effectCADD scoreCDPred scoreGnomAD freq.GnomAD
Allele count / # of het/ # of hom
ClinPred
Score
Age at diagnosis (y):SexPhenotype
(MIM#)
S.18 FBXO38(5:147 785 932)
NM_030793.4:c.843T>G p.His281Gln
Het.23.3000/0/01.0018:MJuvenile-onset upper limb distal weakness; a de novo variant.
HMN2D (615575)
S.4 LAMA2
(6:129 636 905)NM_000426.3: c.3736-2A>T p.(?)
Hom.34−300.000011943/3/0NA69:FChildhood-onset with milder phenotype, retained independent ambulation.
LGMDR23 (618138)
F.3.1; F.3.2 LAMA2(6:129 204 451_129204 452)NM_000426.3:c.61_62delCA
p.Gln21Glyfs*28
Het.20.2−3000/0/0NA34:F; 24:FChildhood-onset with milder phenotype, retained independent ambulation in sisters.
LGMDR23 (618138)
S.13 MFN2
(1:12 052 717)NM_014874.3:c.281G>T p.Arg94Leu
Het.31−200/0/00.9938:FChildhood-onset with severe disease, loss of ambulation by age 30y.
CMT2A (609260)
F.5.1; F.5.2 MFN2
(1:12 062 085)
NM_014874.3:c.1085C>G p.Thr362Arg
Het.24.3−100/0/00.9933:M;60:FAdult-onset with milder, later onset disease in proband and his maternal aunt.
CMT2A (609260)
S.7 MYH7(14:23 886 123)
NM_000257.2:c.4598T>C p.Leu1533Pro
Het.30−900/0/00.9965:MChildhood-onset with foot drop at age 6 years. Loss of ambulation during his late 50s. A de novo variant.
Laing distal myopathy (160500)
S.15 PNPLA6(19:7 615 957)NM_006702.4:c.2031G>T p.Glu677Asp;
PNPLA6
(19:7 619 463)NM_006702.4:c.2374G>C p.Gly792Arg
Comp.
het.
17.8;23.6−3;
−2
0.00000679;0.000063771/1/0;2/2/00.18;0.9219:FJuvenile-onset motor neuron disease with upper >lower limb distal weakness; absent spasticity.
S.14 SPTLC1(19:7 619 463)
NM_006415.2:c.1019C>T p.Ser340Leu
Het.23.6−20.000015924/4/00.9268:MLate-onset hereditary motor sensory neuropathy with mixed sensory and motor symptoms.