Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24686 | 74281;74282;74283 | chr2:178572076;178572075;178572074 | chr2:179436803;179436802;179436801 |
| N2AB | 23045 | 69358;69359;69360 | chr2:178572076;178572075;178572074 | chr2:179436803;179436802;179436801 |
| N2A | 22118 | 66577;66578;66579 | chr2:178572076;178572075;178572074 | chr2:179436803;179436802;179436801 |
| N2B | 15621 | 47086;47087;47088 | chr2:178572076;178572075;178572074 | chr2:179436803;179436802;179436801 |
| Novex-1 | 15746 | 47461;47462;47463 | chr2:178572076;178572075;178572074 | chr2:179436803;179436802;179436801 |
| Novex-2 | 15813 | 47662;47663;47664 | chr2:178572076;178572075;178572074 | chr2:179436803;179436802;179436801 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs727504921  |
-0.395 | 0.985 | N | 0.696 | 0.271 | 0.439018943094 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| S/C | rs727504921 |
-0.395 | 0.985 | N | 0.696 | 0.271 | 0.439018943094 | gnomAD-4.0.0 | 6.36981E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.73329E-05 | 0 |
| S/F | rs727504921 |
-0.509 | 0.034 | N | 0.639 | 0.171 | 0.377451072189 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 1.66722E-04 |
| S/F | rs727504921 |
-0.509 | 0.034 | N | 0.639 | 0.171 | 0.377451072189 | gnomAD-4.0.0 | 6.36981E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14389E-05 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0884 | likely_benign | 0.0821 | benign | -0.778 | Destabilizing | 0.019 | N | 0.442 | neutral | N | 0.47628825 | None | None | N |
| S/C | 0.0867 | likely_benign | 0.0807 | benign | -0.303 | Destabilizing | 0.985 | D | 0.696 | prob.neutral | N | 0.472422423 | None | None | N |
| S/D | 0.5012 | ambiguous | 0.4492 | ambiguous | -1.122 | Destabilizing | 0.664 | D | 0.637 | neutral | None | None | None | None | N |
| S/E | 0.5679 | likely_pathogenic | 0.5521 | ambiguous | -0.897 | Destabilizing | 0.846 | D | 0.618 | neutral | None | None | None | None | N |
| S/F | 0.155 | likely_benign | 0.1302 | benign | -0.483 | Destabilizing | 0.034 | N | 0.639 | neutral | N | 0.455163616 | None | None | N |
| S/G | 0.132 | likely_benign | 0.1134 | benign | -1.188 | Destabilizing | 0.601 | D | 0.576 | neutral | None | None | None | None | N |
| S/H | 0.255 | likely_benign | 0.2354 | benign | -1.309 | Destabilizing | 0.991 | D | 0.695 | prob.neutral | None | None | None | None | N |
| S/I | 0.1088 | likely_benign | 0.0973 | benign | 0.283 | Stabilizing | 0.881 | D | 0.715 | prob.delet. | None | None | None | None | N |
| S/K | 0.6784 | likely_pathogenic | 0.6477 | pathogenic | 0.128 | Stabilizing | 0.936 | D | 0.606 | neutral | None | None | None | None | N |
| S/L | 0.0714 | likely_benign | 0.0645 | benign | 0.283 | Stabilizing | 0.019 | N | 0.523 | neutral | None | None | None | None | N |
| S/M | 0.1173 | likely_benign | 0.1089 | benign | 0.018 | Stabilizing | 0.194 | N | 0.425 | neutral | None | None | None | None | N |
| S/N | 0.1172 | likely_benign | 0.1048 | benign | -0.576 | Destabilizing | 0.001 | N | 0.285 | neutral | None | None | None | None | N |
| S/P | 0.9284 | likely_pathogenic | 0.9092 | pathogenic | -0.038 | Destabilizing | 0.955 | D | 0.735 | prob.delet. | N | 0.494881544 | None | None | N |
| S/Q | 0.4096 | ambiguous | 0.3921 | ambiguous | -0.282 | Destabilizing | 0.936 | D | 0.669 | neutral | None | None | None | None | N |
| S/R | 0.5796 | likely_pathogenic | 0.5475 | ambiguous | -0.324 | Destabilizing | 0.936 | D | 0.737 | prob.delet. | None | None | None | None | N |
| S/T | 0.069 | likely_benign | 0.0661 | benign | -0.269 | Destabilizing | 0.005 | N | 0.277 | neutral | N | 0.462278802 | None | None | N |
| S/V | 0.1198 | likely_benign | 0.1094 | benign | -0.038 | Destabilizing | 0.532 | D | 0.686 | prob.neutral | None | None | None | None | N |
| S/W | 0.3215 | likely_benign | 0.2684 | benign | -0.739 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| S/Y | 0.1517 | likely_benign | 0.1268 | benign | -0.262 | Destabilizing | 0.951 | D | 0.746 | deleterious | N | 0.457414487 | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.