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Table 1 Mutational spectrum of 11 subjects from 10 families with DFNB9

From: Mutational and phenotypic spectrum of OTOF-related auditory neuropathy in Koreans: eliciting reciprocal interaction between bench and clinics

Family ID Variant (OTOF)
NM_001287489
NP_001274418
State Prediction algorithm Conservation score MAF Classification of pathogenic variants [31] References
Mutation taster PolyPhen-2 SIFT PhyloP GERP++ Global MAF KRGDB (n = 1722)
SB10-23 c.5816G > A: p.Arg1939Gln
rs201326023
Hom DC PD D 2.261 2.28 T = 0.00003/1 (ExAC)
T = 0.0002/1 (1000 Genomes)
T = 0.001452/5 Pathogenic
(PS4, PM2, PM3
PP1, PP3, PP4)
[31]
SH132-273 c.5816G > A: p.Arg1939Gln
rs201326023
Hom DC PD D 2.261 2.28 T = 0.00003/1 (ExAC)
T = 0.0002/1 (1000 Genomes)
T = 0.001452/5 Pathogenic [31]
SB22-51 c.5816G > A: p.Arg1939Gln
rs201326023
Het DC PD D 2.261 2.28 T = 0.00003/1 (ExAC)
T = 0.0002/1 (1000 Genomes)
T = 0.001452/5 Pathogenic [31]
Large genomic deletion Chr2:26710657 ~ 26706557 Het NA NA NA NA NA    Pathogenic (PVS1, PP1, PP4) [16]
SB204-398 c.5816G > A: p.Arg1939Gln
rs201326023
Het DC PD D 2.261 2.28 T = 0.00003/1 (ExAC)
T = 0.0002/1 (1000 Genomes)
T = 0.001452/5 Pathogenic [31]
c.5566C > T: p.Arg1856Trp
rs368155547
Het DC PD D 2.963 2.84 A = 0.00004/5 (ExAC)
A = 0.00008/1 (GO-ESP)
A = 0.000871/3 Pathogenic
(PS4, PM2, PM3
PP1, PP3, PP4)
[10]
SH81-185 c.5816G > A: p.Arg1939Gln
rs201326023
Het DC PD D 2.261 2.28 T = 0.00003/1 (ExAC)
T = 0.0002/1 (1000 Genomes)
T = 0.001452/5 Pathogenic [31]
c.2521G > A: p.Glu841Lys
rs772729658
Het DC PD D 5.523 5 T = 0.00003/3 (ExAC) ND Pathogenic
(PS4, PM2, PM3
PP1, PP3, PP4)
[16]
SB239-465 c.5816G > A: p.Arg1939Gln
rs201326023
Het DC PD D 2.261 2.28 T = 0.00003/1 (ExAC)
T = 0.0002/1 (1000 Genomes)
T = 0.001452/5 Pathogenic [31]
c.3032T > C: p.Leu1011Pro
rs80356596
Het DC PD D 5.012 4.64 ND ND Pathogenic
(PS4, PM2, PM3
PP1, PP3, PP4)
[32]
SB239-466 ac.5791C > A: p.Pro1931Thr rs537706054 Het DC PD D 5.867 5.22 T = 0.000008/1 (ExAC) ND Pathogenic
(PM2, PM3,
PP1, PP3, PP4)
This study
c.2521G > A: p.Glu841Lys
rs772729658
Het DC PD D 5.523 5 T = 0.00003/3 (ExAC) ND Pathogenic [16]
SH195-443 c.3192C > G: p.Tyr1064Ter
rs766819324
Hom DC NA NA 1.937 2.78 C = 0.000008/1 (ExAC) C = 0.00029/1 Pathogenic (PVS1, PM2, PP1, PP3, PP4) [15]
SH234-547 c.5816G > A: p.Arg1939Gln
rs201326023
Het DC PD D 2.261 2.28 T = 0.00003/1 (ExAC)
T = 0.0002/1 (1000 Genomes)
T = 0.001452/5 Pathogenic [31]
c.5566C > T: p.Arg1856Trp
rs368155547
Het DC PD D 2.963 2.84 A = 0.00004/5 (ExAC)
A = 0.00008/1 (GO-ESP)
A = 0.000871/3 Pathogenic [10]
AJ2-3 ac.5534G > A: p.Gly1845Glu
dbSNP ID:ND
Het DC PD D 5.739 4.97 ND ND Pathogenic
(PM2, PM3
PP1, PP3, PP4)
This study
c.3032T > C: p.Leu1011Pro
rs80356596
Het DC PD D 5.012 4.64 ND ND Pathogenic [32]
SH230-538 c.2521G > A: p.Glu841Lys
rs772729658
Het DC PD D 5.523 5 T = 0.00003/3 (ExAC) ND Pathogenic [16]
ac.4227 + 5G > C
rs571671530
Het DC NA NA 1.616 3.95 G = 0.00006/7 (ExAC)
G = 0.0002/1 (1000 Genomes)
ND Likely pathogenic (PM2, PM3
PP1, PP3, PP4)
This study
  1. Splice site variant prediction tools by ESEfinder, NNSplice, and NetGene2: splice site broken. Normal score (10.34940) and mutant score (6.54650) by ESEfinder, Normal score (0.99) and mutant score (0.50) by NNSplice, Normal score (0.997) and mutant score (0.685) by NetGene2
  2. In silico prediction Algorithm: Polyphen-2 (http://genetics.bwh.harvard.edu/pph2/index.shtml); SIFT (http://sift.jcvi.org/www/SIFT_chr_coords_submit.html) or SIFT-indels2 (http://sift.bii.a-star.edu.sg/www/SIFT_indels2.html)
  3. Conservation tools: GERP++ score in the UCSC Genome Browser (http://genome-asia.ucsc.edu/); PhyloP score from the Mutation Taster (http://www.mutationtaster.org/)
  4. Splice site prediction tools: ESEfinder (http://rulai.cshl.edu/cgi-bin/tools/ESE3/esefinder.cgi?process=home); NNSplice (http://www.fruitfly.org/seq_tools/splice.html); NetGene2 (http://www.cbs.dtu.dk/services/NetGene2/)
  5. ExAC, Exome Aggregation Consortium (http://exac.broadinstitute.org/)
  6. 1000 Genomes (https://www.ncbi.nlm.nih.gov/variation/tools/1000genomes/)
  7. KRGDB, Korean Reference Genome DB (http://152.99.75.168/KRGDB/)
  8. Het, heterozygote mutant; Hom, homozygote mutant; DC, disease causing; PD, probably damaging; D, damaging; ND, not detected; NA, not applicable
  9. aNovel variant