Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33089 | 99490;99491;99492 | chr2:178538564;178538563;178538562 | chr2:179403291;179403290;179403289 |
| N2AB | 31448 | 94567;94568;94569 | chr2:178538564;178538563;178538562 | chr2:179403291;179403290;179403289 |
| N2A | 30521 | 91786;91787;91788 | chr2:178538564;178538563;178538562 | chr2:179403291;179403290;179403289 |
| N2B | 24024 | 72295;72296;72297 | chr2:178538564;178538563;178538562 | chr2:179403291;179403290;179403289 |
| Novex-1 | 24149 | 72670;72671;72672 | chr2:178538564;178538563;178538562 | chr2:179403291;179403290;179403289 |
| Novex-2 | 24216 | 72871;72872;72873 | chr2:178538564;178538563;178538562 | chr2:179403291;179403290;179403289 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.016 | N | 0.391 | 0.08 | 0.492611691308 | gnomAD-4.0.0 | 1.59438E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43715E-05 | 0 |
| M/T | rs1445903275  |
0.63 | 0.181 | N | 0.355 | 0.13 | 0.535054060289 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| M/T | rs1445903275 |
0.63 | 0.181 | N | 0.355 | 0.13 | 0.535054060289 | gnomAD-4.0.0 | 1.59358E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02737E-05 |
| M/V | rs1181148072 |
0.456 | None | N | 0.163 | 0.122 | 0.402614778071 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 1.00523E-04 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/V | rs1181148072 |
0.456 | None | N | 0.163 | 0.122 | 0.402614778071 | gnomAD-4.0.0 | 4.78004E-06 | None | None | None | None | I | None | 0 | 0 | None | 4.7824E-05 | 0 | None | 0 | 0 | 5.72279E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.2473 | likely_benign | 0.2296 | benign | -0.141 | Destabilizing | 0.057 | N | 0.341 | neutral | None | None | None | None | I |
| M/C | 0.6784 | likely_pathogenic | 0.7034 | pathogenic | -0.465 | Destabilizing | 0.887 | D | 0.368 | neutral | None | None | None | None | I |
| M/D | 0.8392 | likely_pathogenic | 0.7396 | pathogenic | 0.425 | Stabilizing | 0.676 | D | 0.523 | neutral | None | None | None | None | I |
| M/E | 0.553 | ambiguous | 0.4806 | ambiguous | 0.366 | Stabilizing | 0.676 | D | 0.461 | neutral | None | None | None | None | I |
| M/F | 0.3196 | likely_benign | 0.3199 | benign | -0.117 | Destabilizing | 0.507 | D | 0.337 | neutral | None | None | None | None | I |
| M/G | 0.4843 | ambiguous | 0.4265 | ambiguous | -0.23 | Destabilizing | 0.373 | N | 0.482 | neutral | None | None | None | None | I |
| M/H | 0.5676 | likely_pathogenic | 0.5522 | ambiguous | 0.411 | Stabilizing | 0.96 | D | 0.449 | neutral | None | None | None | None | I |
| M/I | 0.3183 | likely_benign | 0.2789 | benign | -0.005 | Destabilizing | 0.016 | N | 0.391 | neutral | N | 0.510771756 | None | None | I |
| M/K | 0.2531 | likely_benign | 0.2651 | benign | 0.429 | Stabilizing | 0.31 | N | 0.404 | neutral | N | 0.483916016 | None | None | I |
| M/L | 0.1314 | likely_benign | 0.1243 | benign | -0.005 | Destabilizing | 0.009 | N | 0.265 | neutral | N | 0.481662358 | None | None | I |
| M/N | 0.4881 | ambiguous | 0.4015 | ambiguous | 0.511 | Stabilizing | 0.864 | D | 0.491 | neutral | None | None | None | None | I |
| M/P | 0.8412 | likely_pathogenic | 0.6603 | pathogenic | -0.027 | Destabilizing | 0.864 | D | 0.459 | neutral | None | None | None | None | I |
| M/Q | 0.2777 | likely_benign | 0.2746 | benign | 0.385 | Stabilizing | 0.864 | D | 0.358 | neutral | None | None | None | None | I |
| M/R | 0.2812 | likely_benign | 0.3032 | benign | 0.814 | Stabilizing | 0.612 | D | 0.412 | neutral | N | 0.460673797 | None | None | I |
| M/S | 0.3187 | likely_benign | 0.2674 | benign | 0.112 | Stabilizing | 0.227 | N | 0.319 | neutral | None | None | None | None | I |
| M/T | 0.1436 | likely_benign | 0.1319 | benign | 0.142 | Stabilizing | 0.181 | N | 0.355 | neutral | N | 0.426155792 | None | None | I |
| M/V | 0.0786 | likely_benign | 0.0678 | benign | -0.027 | Destabilizing | None | N | 0.163 | neutral | N | 0.459113572 | None | None | I |
| M/W | 0.7528 | likely_pathogenic | 0.7745 | pathogenic | -0.154 | Destabilizing | 0.96 | D | 0.385 | neutral | None | None | None | None | I |
| M/Y | 0.6214 | likely_pathogenic | 0.6316 | pathogenic | 0.056 | Stabilizing | 0.676 | D | 0.405 | neutral | None | None | None | None | I |
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.