Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15062 | 45409;45410;45411 | chr2:178621640;178621639;178621638 | chr2:179486367;179486366;179486365 |
| N2AB | 13421 | 40486;40487;40488 | chr2:178621640;178621639;178621638 | chr2:179486367;179486366;179486365 |
| N2A | 12494 | 37705;37706;37707 | chr2:178621640;178621639;178621638 | chr2:179486367;179486366;179486365 |
| N2B | 5997 | 18214;18215;18216 | chr2:178621640;178621639;178621638 | chr2:179486367;179486366;179486365 |
| Novex-1 | 6122 | 18589;18590;18591 | chr2:178621640;178621639;178621638 | chr2:179486367;179486366;179486365 |
| Novex-2 | 6189 | 18790;18791;18792 | chr2:178621640;178621639;178621638 | chr2:179486367;179486366;179486365 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs373627060  |
-1.723 | None | N | 0.178 | 0.23 | None | gnomAD-2.1.1 | 5.66E-05 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 3.92311E-04 | None | 0 | 0 | 1.66556E-04 |
| I/T | rs373627060 |
-1.723 | None | N | 0.178 | 0.23 | None | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.1632E-04 | 0 |
| I/T | rs373627060 |
-1.723 | None | N | 0.178 | 0.23 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| I/T | rs373627060 |
-1.723 | None | N | 0.178 | 0.23 | None | gnomAD-4.0.0 | 2.29474E-05 | None | None | None | None | N | None | 2.67051E-05 | 0 | None | 0 | 2.23954E-05 | None | 0 | 0 | 1.69627E-06 | 3.40562E-04 | 1.60251E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1473 | likely_benign | 0.138 | benign | -1.864 | Destabilizing | None | N | 0.174 | neutral | None | None | None | None | N |
| I/C | 0.4647 | ambiguous | 0.4702 | ambiguous | -0.858 | Destabilizing | 0.245 | N | 0.445 | neutral | None | None | None | None | N |
| I/D | 0.3303 | likely_benign | 0.3034 | benign | -1.642 | Destabilizing | 0.018 | N | 0.485 | neutral | None | None | None | None | N |
| I/E | 0.2626 | likely_benign | 0.2544 | benign | -1.567 | Destabilizing | 0.018 | N | 0.419 | neutral | None | None | None | None | N |
| I/F | 0.1117 | likely_benign | 0.0994 | benign | -1.192 | Destabilizing | 0.033 | N | 0.467 | neutral | N | 0.451106007 | None | None | N |
| I/G | 0.3361 | likely_benign | 0.3249 | benign | -2.244 | Highly Destabilizing | 0.009 | N | 0.382 | neutral | None | None | None | None | N |
| I/H | 0.2263 | likely_benign | 0.2237 | benign | -1.457 | Destabilizing | 0.497 | N | 0.524 | neutral | None | None | None | None | N |
| I/K | 0.1445 | likely_benign | 0.1393 | benign | -1.303 | Destabilizing | None | N | 0.393 | neutral | None | None | None | None | N |
| I/L | 0.0875 | likely_benign | 0.0853 | benign | -0.849 | Destabilizing | 0.001 | N | 0.3 | neutral | N | 0.463343052 | None | None | N |
| I/M | 0.0842 | likely_benign | 0.0808 | benign | -0.572 | Destabilizing | 0.108 | N | 0.445 | neutral | N | 0.485075368 | None | None | N |
| I/N | 0.1101 | likely_benign | 0.097 | benign | -1.231 | Destabilizing | 0.014 | N | 0.493 | neutral | N | 0.486317561 | None | None | N |
| I/P | 0.7235 | likely_pathogenic | 0.632 | pathogenic | -1.16 | Destabilizing | 0.085 | N | 0.553 | neutral | None | None | None | None | N |
| I/Q | 0.1769 | likely_benign | 0.1871 | benign | -1.34 | Destabilizing | 0.044 | N | 0.561 | neutral | None | None | None | None | N |
| I/R | 0.1112 | likely_benign | 0.1035 | benign | -0.736 | Destabilizing | None | N | 0.393 | neutral | None | None | None | None | N |
| I/S | 0.1184 | likely_benign | 0.1061 | benign | -1.818 | Destabilizing | 0.001 | N | 0.305 | neutral | N | 0.394927337 | None | None | N |
| I/T | 0.087 | likely_benign | 0.0702 | benign | -1.63 | Destabilizing | None | N | 0.178 | neutral | N | 0.344113597 | None | None | N |
| I/V | 0.0708 | likely_benign | 0.071 | benign | -1.16 | Destabilizing | None | N | 0.129 | neutral | N | 0.424741259 | None | None | N |
| I/W | 0.5684 | likely_pathogenic | 0.5236 | ambiguous | -1.394 | Destabilizing | 0.788 | D | 0.529 | neutral | None | None | None | None | N |
| I/Y | 0.297 | likely_benign | 0.2958 | benign | -1.132 | Destabilizing | 0.085 | N | 0.524 | neutral | None | None | 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.