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Table 1 Pathogenic or likely pathogenic variants detected in this study

From: Contribution of gene mutations to Silver-Russell syndrome phenotype: multigene sequencing analysis in 92 etiology-unknown patients

PatientPathogenic or likely pathogenic variants in the responsible genes for SRSPathogenic variants in causative genes for known genetic syndromes presenting with growth failure
Patient 1 [12]Patient 2 [12]Patient 3Patient 4Patient 5Patient 6Patient 7Patient 8Patient 9
GeneIGF2IGF2CDKN1CPLAG1IGF1RPIK3R1SRCAPTCF4PTPN11
Variantc.209G>Ac.211T>Cc.947G>Ac.589C>Tc.1457delCc.1892G>Ac.7376delCc.1102_1103delCAc.844A>G
p.(Cys70Tyr)p.(Cys71Arg)p.(Arg316Gln)p.(Arg197*)p.(Ser487Profs*21)p.(Arg631Gln)p.(Pro2459Leufs*16)p.(Gln368Glyfs*6)p.(Ile282Val)
Genetic diagnosisSRSSRSSRSSRSIGF1R abnormalitySHORT syndromeFloating-Harbor syndromePitt-Hopkins syndromeNoonan syndrome
InheritanceDe novoDe novo or paternalMother (carrier)Mother (affected)Father (carrier)De novoDe novoDe novoDe novo
AllelePaternalPaternalMaternalMaternalPaternalNENENENE
Karyotype46,XY46,XY46,XX46,XXNE46,XY46,XY46,XX46,XY
Allele frequency
 gnomAD [13]NoneNoneNoneNoneNoneNoneNoneNoneNone
 HGVD [14]NoneNoneNoneNoneNoneNoneNoneNoneNone
 4.7KJPN [15]NoneNoneNoneNoneNoneNoneNoneNoneNone
In silico pathogenicity prediction
 CADD [16]1% most deleterious1% most deleterious1% most deleterious1% most deleterious1% most deleterious1% most deleterious1% most deleterious1% most deleterious1% most deleterious
 (PHRED score)27.427.232.037.035.033.027.235.023.6
 MutationTaster [17] (score)Disease causingDisease causingDisease causingDisease causingDisease causingDisease causingDisease causingDisease causingDisease causing
1.0001.0000.6621.0001.0001.0001.0001.0001.000
 SIFT [18] (score)DamagingDamagingDamagingDamagingDamaging
0.0000.0000.000  0.000  0.000
 PP2_HVAR [19] (score)Probably damagingProbably damagingProbably damagingProbably damagingBenign
0.9750.9330.982  0.941  0.088
 M-CAP [20] (score)Possibly pathogenicPossibly pathogenicPossibly pathogenicPossible pathogenicPossibly pathogenic
0.8670.8870.964  0.568  0.033
ACMG classification [11] criteriaPathogenicLikely pathogenicLikely pathogenicPathogenicPathogenicPathogenicPathogenicPathogenicPathogenic
PS2, PM1, PM2, PP3, PP4PM1, PM2, PP3, PP4PS3, PM2, PM5a, PP3PVS1, PM2, PP1, PP3PVS1, PM2, PP3PS1, PS2, PM2, PP3PSV1, PS1, PS2, PM2, PP3PSV1, PS2, PM2, PP3, PP4PS1, PS2, PM2
  1. Accession number IGF2 NM_000612.6, CDKN1C NM_000076.2, PLAG1 NM_002655.3, IGF1R NM_000875.5, PIK3R1 NM_181523.3, SRCAP NM_006662.3, TCF4 NM_001083962.2, and PTPN11 NM_002834.5
  2. SRS Silver-Russell syndrome, NE not examined, gnomAD Genome Aggregation Database, HGVD Human Genetic Variation Database, 4.7KJPN allele and genotype frequency panel from 4.7 K Japanese individuals, CADD Combined Annotation Dependent Depletion, SIFT Sorting Intolerant From Tolerant, PP2 Polymorphism Phenotyping v2, M-CAP Mendelian Clinically Applicable Pathogenicity
  3. aA different missense variant (p.(Arg316Trp)) was reported in a patient with Bechwith-Wiedemann syndrome [21]