Table 3 .
In silico analysis of long QT genetic variants found in eight victims of SIDS
Gene | RefSeq accession numbers (transcript and protein) and UniProt number | Variant position (transcript, protein and exon) | Bioinformatic programmes | Interpretation | ||||||
---|---|---|---|---|---|---|---|---|---|---|
PolyPhen-2a,* | Mutation Assessorb (Functional Impact) | I-MUTANT 3.0c | PMutd | MutPrede | SNPs&GOf | PANTHERg | ||||
KCNQ1 |
NM_000218.2 NP_000209.2 P51787 |
c.436G>A p.E146K E2 |
Benign (Scores: 0.250; 0.134) | Neutral | Disease (RI 6.0) | Neutral (RS 0) | Pdel: 0.859 | Disease (RI 5.0) | Pdel: 0.31 | Pathogenic (LQTS1) |
KCNH2 |
NM_000238.2 NP_000229.1 Q12809 |
c.3140G>T p.R1047L E13 |
Benign (Scores: 0.039; 0.020) | Low | Disease (RI 2.0) | Pathological (RS 8) | Pdel: 0.373 | Disease (RI 1.0) | Pdel: 0.42 | Pathogenic (LQTS2) |
SCN5A |
NM_198056.2 NP_932173.1 Q14524 |
c.1673A>G p.H558R E6 |
Benign (Scores: 0.000; 0.000) | Neutral | Neutral (RI 6.0) | Neutral (RS 6) | Pdel: 0.086 | Neutral (RI 8.0) | Pdel: 0.14 | Polymorphism |
c.2275A>T† p.I759F E15 |
Benign (Scores: 0.003; 0.007) | Medium | Disease (RI 5.0) | Neutral (RS 3) | Pdel: 0.878 | Disease (RI 7.0) | Pdel: 0.54 | Pathogenic (LQTS3) | ||
c.3578G>A p.R1193Q E20 |
Benign (Scores: 0.001; 0.006) | Low‡ | Disease (RI 6.0) | Pathological (RS 3) | Pdel: 0.825 | Neutral (RI 4.0) | Pdel: 0.28 | Uncertain | ||
c.4565T>A† p.F1522Y E27 |
Benign (Scores: 0.417; 0.116) | Low | Neutral (RI 1.0) | Neutral (RS 8) | Pdel: 0.823 | Disease (RI 4.0) | – | Possibly pathogenic (LQTS3) |
c. http://gpcr2.biocomp.unibo.it/cgi/predictors/I-Mutant3.0/I-Mutant3.0.cgi; RI refers to Reliability Index.
d. http://mmb2.pcb.ub.es:8080/PMut/; RS refers to Reliability Score.
e. http://mutpred.mutdb.org/; Pdel refers to the probability that the variant is a deleterious mutation.
f. http://snps-and-go.biocomp.unibo.it/snps-and-go/; RI refers to Reliability Index.
g. http://www.pantherdb.org/tools/csnpScoreForm.jsp; Pdel refers to the probability that a given variant will cause a deleterious effect on protein function.
*Scores relate to predictions based on HumDiv and HumVar models.
†Not previously reported.
‡Accelerates the inactivation of the sodium channel current and exhibits reduced sodium channel current at the end of phase I of the action potential (taken from report provided by Mutation Assessor).
LQTS, long QT syndrome; SIDS, sudden infant death syndrome.