ABCA4 p.Val1393Ile
| Predicted by SNAP2: | A: N (66%), C: N (66%), D: D (66%), E: N (61%), F: N (53%), G: D (63%), H: N (61%), I: N (93%), K: N (53%), L: N (82%), M: N (78%), N: N (57%), P: D (53%), Q: N (61%), R: N (53%), S: N (57%), T: N (78%), W: D (75%), Y: N (53%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] Analysis of the ABCA4 gene by next-generation sequ... Invest Ophthalmol Vis Sci. 2011 Oct 31;52(11):8479-87. doi: 10.1167/iovs.11-8182. Zernant J, Schubert C, Im KM, Burke T, Brown CM, Fishman GA, Tsang SH, Gouras P, Dean M, Allikmets R
Analysis of the ABCA4 gene by next-generation sequencing.
Invest Ophthalmol Vis Sci. 2011 Oct 31;52(11):8479-87. doi: 10.1167/iovs.11-8182., [PMID:21911583]
Abstract [show]
PURPOSE: To find all possible disease-associated variants in coding sequences of the ABCA4 gene in a large cohort of patients diagnosed with ABCA4-associated diseases. METHODS: One hundred sixty-eight patients who had been clinically diagnosed with Stargardt disease, cone-rod dystrophy, and other ABCA4-associated phenotypes were prescreened for mutations in ABCA4 with the ABCA4 microarray, resulting in finding 1 of 2 expected mutations in 111 patients and 0 of 2 mutations in 57 patients. The next-generation sequencing (NGS) strategy was applied to these patients to sequence the entire coding region and the splice sites of the ABCA4 gene. Identified new variants were confirmed or rejected by Sanger sequencing and analyzed for possible pathogenicity by in silico programs and, where possible, by segregation analyses. RESULTS: Sequencing was successful in 159 of 168 patients and identified the second disease-associated allele in 49 of 103 (~48%) of patients with one previously identified mutation. Among those with no mutations, both disease-associated alleles were detected in 4 of 56 patients, and one mutation was detected in 10 of 56 patients. The authors detected a total of 57 previously unknown, possibly pathogenic, variants: 29 missense, 4 nonsense, 9 small deletions and 15 splice-site-altering variants. Of these, 55 variants were deemed pathogenic by a combination of predictive methods and segregation analyses. CONCLUSIONS: Many mutations in the coding sequences of the ABCA4 gene are still unknown, and many possibly reside in noncoding regions of the ABCA4 locus. Although the ABCA4 array remains a good first-pass screening option, the NGS platform is a time- and cost-efficient tool for screening large cohorts.
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No. Sentence Comment
120 Novel Variants Detected by NGS in the ABCA4 Gene and Results of Analysis Using Bioinformatics Software Nucleotide Change Protein Splicing Score Original Splicing Score for New Variant Average Difference Polyphen SIFT SpliceSite Finder-like Gene Splicer SpliceSite Finder-like Gene Splicer c.91Tb0e;C p.W31R 0 0 0 0 0 Probably damaging (0.999) W c.184Cb0e;T p.P62S 0 0 0 0 0 Probably damaging (0.999) P c.770Tb0e;G p.L257R 0 0 0 0 0 Possibly damaging (0.308) m i F L c.1253Tb0e;C p.F418S 0 0 0 0 0 Probably damaging (0.999) F c.1531Cb0e;T p.R511C 0 0 0 0 0 Probably damaging (1.000) R c.1745Ab0e;G p.N582S 0 0 0.74 0.82 77.8 Probably damaging (0.894) d K N c.1868Ab0e;G p.Q623R 0 0.24 0 0 12.1 Probably damaging (0.937) Q c.1964Tb0e;G p.F655C 0 0 0 0 0 Probably damaging (0.999) F c.1977Gb0e;A p.M659I 0 0 0.75 0.85 79.8 Probably damaging (0.999) M c.2243Gb0e;A p.C748Y 0 0 0 0 0 Probably damaging (0.928) g S A C c.2401Gb0e;A p.A801T 0 0 0 0 0 Probably damaging (0.98) A c.2893Ab0e;T p.N965Y 0 0 0 0 0 Probably damaging (0.999) N c.3148Gb0e;A p.G1050S 0 0 0 0 0 Possibly damaging (0.786) G c.3205Ab0e;G p.K1069E 0 0 0 0 0 Probably damaging (0.993) K c.3279Cb0e;A p.D1093E 0 0 0 0 0 Probably damaging (0.99) D c.3350Cb0e;T p.T1117I 0 0 0 0 0 Probably damaging (0.995) T c.3655Gb0e;C p.A1219P 0.77 0 0.74 0 1.5 Probably damaging (0.991) A c.3812Ab0e;G p.E1271G 0.8 0.35 0.71 0 21.8 Probably damaging (0.995) E c.4177Gb0e;A p.V1393I 0 0 0 0 0 Benign (0.000) VI c.4217Ab0e;G p.H1406R 0 0 0 0 0 Probably damaging (0.986) r p q a t k e g n S D H c.4248Cb0e;A p.F1416L 0.79 0.1 0.79 0.1 0.27 Probably damaging (0.891) F c.4326Cb0e;A p.N1442K 0 0 0 0 0 Possibly damaging (0.374) a g d s T N c.4467Gb0e;T p.R1489S 0.85 0.43 0.78 0.24 12.8 Benign (0.047) p h l s n a e T Q K R c.4670Ab0e;G p.Y1557C 0.85 0.13 0.80 0 8.8 Probably damaging (0.999) f W Y c.5138Ab0e;G p.Q1713R 0 0 0 0 0 Probably damaging (0.997) Q c.5177Cb0e;A p.T1726N 0 0 0 0 0 Probably damaging (0.880) s A T c.5646Gb0e;A p.M1882I 0 0 0.75 0 37.4 Probably damaging (0.999) M c.6306Cb0e;A p.D2102E 0 0 0 0 0 Probably damaging (0.99) D c.6718Ab0e;G p.T2240A 0 0 0 0 0 Probably damaging (0.991) T c.160af9;2Tb0e;C 0.81 0.86 0.79 0 44.4 c.1240afa;2Ab0e;G 0.82 0.81 0 0 81.5 c.2382af9;1Gb0e;A 0.79 0.64 0 0 71.7 c.2919afa;2Ab0e;G 0.9 0.92 0 0 90.9 c.3522af9;5delG 0.87 0.57 0 0.18 63 c.3523afa;1Gb0e;A 0.9 0.89 0 0 89 Splice site shift of 1 bp c.3814afa;2Ab0e;G 0.91 0.9 0 0 90.6 c.4352af9;1Gb0e;A 0.74 0.82 0 0 78 c.4635afa;1Gb0e;T 0.86 0.89 0 0 87.5 New splice site 7 bp downstream c.5312af9;1Gb0e;A 0.81 0.91 0 0 86.1 c.5836afa;2Ab0e;C 0.89 0.87 0 0 88 c.6387afa;1Gb0e;T 0.77 0.87 0 0 82 c.6479af9;1Gb0e;A 0.82 0.87 0 0 85 c.6479af9;1Gb0e;C 0.82 0.31 0 0 56.6 c.1100afa;6Tb0e;A 0 0 0.9 0.93 91.6 Creates new splice site c.351_352delAG p.S119fs Frameshift c.564delA p.E189Cfs Frameshift c.885delC p.L296Cfs Frameshift c.1374delA p.T459Qfs Frameshift c.3543delT p.K1182Rfs Frameshift c.3846delA p.G1283Dfs Frameshift c.4734delG p.L1580* Stop codon c.5932delA p.T1979Qfs Frameshift c.6317_6323del p.R2107_ GCCGCAT M2108delfs Frameshift c.121Gb0e;A p.W41* Stop codon c.318Tb0e;G p.Y106* Stop codon c.1906Cb0e;T p.Q636* Stop codon c.4639Ab0e;T p.K1547* Stop codon For SpliceSiteFinder and GeneSplicer, 1 is the highest score for splice site activity and 0 is the lowest.
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ABCA4 p.Val1393Ile 21911583:120:1480
status: NEW136 11 Deep Sequencing of the ABCA4 Gene doi:10.1167/iovs.11-8182/-/DCSupplemental), including two novel rare variants p.V1393I and p.R1489S (both detected once) that were predicted to be tolerated.
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ABCA4 p.Val1393Ile 21911583:136:119
status: NEW