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Table 3 Rare variants observed in CMT-related genes from patients in the five Pakistani CMT families

From: Novel homozygous mutations in Pakistani families with Charcot–Marie–Tooth disease

Family Gene Variant ClinVar dbSNP151 Allele frequency GERP In silico analysisa Note
Nucleotide Amino acid 1000G gnomAD PP2 PRO Fath
PaC2 KIF1B c.3209C > T p.A1070V UR rs768176241 UR 1.8E−05 4.82 0.02 − 0.01 − 0.77 Nonsegregation, LB
  DST [c.7252G > A + c.7765A > G] [p.V2418I + p.I2589V] UR rs62621210 0.0400 0.0360 4.80 0.00 0.76 1.25 Cis, nonsegregation, LB
     B,LB rs150191284 0.0102 0.0249 4.45 0.02 0.07 − 0.74  
  MYH14 c.3748G > T p.V1250L LB rs202242879 0.0006 0.0007 3.78 0.11 − 0.39 − 1.17 Nonsegregation, LB
  SCN11A c.1732 T > A p.F578I UR rs772393665 UR 7.1E−05 5.58 0.98* − 4.61* − 4.30* Nonsegregation, LB
PaC3 KIF1B [c.2107 T > C] + [c.2455A > C] [p.W703R] + [p.S819R] B,LB rs551543997 0.0054 0.0026 5.32 0.99* − 10.0* − 0.93 Trans, nonsegregation, LB
     LB rs140015591 0.0002 0.0003 − 2.96 0.02 − 2.19 − 1.03  
  NTRK1 [c.2339G > A + c.2360C > T] [p.R780Q + p.A787V] B,LB rs35669708 0.0038 0.0046 4.10 0.87* − 1.25 − 1.60* Cis, nonsegregation, LB
     UR rs761207548 UR 5.0E−05 4.07 0.36 − 3.00* − 1.13  
  NAGLU c.2209C > A p.R737S B rs86312 0.0116 0.0183 4.01 0.47* − 0.19 − 5.34* Nonsegregation, LB
  SCN10A c.3887G > T p.S1296I LB rs779527264 UR 0.0002 4.88 1.00* − 5.79* − 4.55* Nonsegregation, LB
PaC4 DST [c.1933A > G] + [c.1933A > G] [p.I645V] + [p.I645V] UR rs754692637 UR 8.0E−06 2.51 0.00 − 0.20 − 0.81 Homozygous, cosegregation, VUS
  ARHGEF10 c.2566G > A p.V856I UR rs773521162 UR 0.0003 4.25 0.87* − 0.62 0.15 Nonsegregation, LB
PaC6 TFG c.175A > G p.K59E UR rs1232918261 UR UR 5.90 1.00* − 3.02* − 3.02* Nonsegregation, LB
PaC14 SETX c.2385_2387delTTT p.I795_K796delinsM UR rs755971927 UR 5.0E−05 Nonsegregation, LB
  1. 1000G: 1000 Genomes Project, B: benign, gnomAD: Genome Aggregation Database, LB: likely benign, VUS: variant of uncertain significance, trans: trans arrangement of variants in homologous chromosomes (bi-alleles), cis: cis arrangement of variants in a chromosome, UR: unreported
  2. aScores of PolyPhen-2 (PP2) ~ 1, PROVEAN (PRO) < − 2.5, and Fathmm (Fath) < − 1.5 indicate pathogenic prediction (* denotes a pathogenic prediction)