Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15329 | 46210;46211;46212 | chr2:178620536;178620535;178620534 | chr2:179485263;179485262;179485261 |
| N2AB | 13688 | 41287;41288;41289 | chr2:178620536;178620535;178620534 | chr2:179485263;179485262;179485261 |
| N2A | 12761 | 38506;38507;38508 | chr2:178620536;178620535;178620534 | chr2:179485263;179485262;179485261 |
| N2B | 6264 | 19015;19016;19017 | chr2:178620536;178620535;178620534 | chr2:179485263;179485262;179485261 |
| Novex-1 | 6389 | 19390;19391;19392 | chr2:178620536;178620535;178620534 | chr2:179485263;179485262;179485261 |
| Novex-2 | 6456 | 19591;19592;19593 | chr2:178620536;178620535;178620534 | chr2:179485263;179485262;179485261 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs1417624685  |
0.323 | 0.999 | N | 0.698 | 0.361 | 0.329282125956 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/D | rs1417624685 |
0.323 | 0.999 | N | 0.698 | 0.361 | 0.329282125956 | gnomAD-4.0.0 | 1.5947E-06 | None | None | None | None | I | None | 0 | 2.29295E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/I | None | None | 1.0 | D | 0.663 | 0.537 | 0.680558501852 | gnomAD-4.0.0 | 6.84846E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00045E-07 | 0 | 0 |
| N/S | rs371734564 |
0.168 | 0.999 | N | 0.653 | 0.389 | None | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/S | rs371734564 |
0.168 | 0.999 | N | 0.653 | 0.389 | None | gnomAD-4.0.0 | 4.10908E-06 | None | None | None | None | I | None | 2.99473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.60018E-06 | 0 | 1.65893E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.4084 | ambiguous | 0.3218 | benign | -0.408 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| N/C | 0.53 | ambiguous | 0.4985 | ambiguous | 0.252 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| N/D | 0.1959 | likely_benign | 0.1364 | benign | 0.235 | Stabilizing | 0.999 | D | 0.698 | prob.neutral | N | 0.485244726 | None | None | I |
| N/E | 0.5238 | ambiguous | 0.4062 | ambiguous | 0.232 | Stabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | I |
| N/F | 0.7369 | likely_pathogenic | 0.6829 | pathogenic | -0.647 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| N/G | 0.3034 | likely_benign | 0.2513 | benign | -0.621 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | I |
| N/H | 0.1785 | likely_benign | 0.138 | benign | -0.51 | Destabilizing | 1.0 | D | 0.646 | neutral | D | 0.617292697 | None | None | I |
| N/I | 0.6339 | likely_pathogenic | 0.5264 | ambiguous | 0.072 | Stabilizing | 1.0 | D | 0.663 | neutral | D | 0.552477741 | None | None | I |
| N/K | 0.4916 | ambiguous | 0.3273 | benign | 0.063 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.50609908 | None | None | I |
| N/L | 0.4148 | ambiguous | 0.3864 | ambiguous | 0.072 | Stabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| N/M | 0.5486 | ambiguous | 0.5063 | ambiguous | 0.281 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| N/P | 0.6871 | likely_pathogenic | 0.6111 | pathogenic | -0.06 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | I |
| N/Q | 0.4707 | ambiguous | 0.3708 | ambiguous | -0.386 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | I |
| N/R | 0.512 | ambiguous | 0.3919 | ambiguous | 0.097 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| N/S | 0.1514 | likely_benign | 0.1245 | benign | -0.271 | Destabilizing | 0.999 | D | 0.653 | neutral | N | 0.503218333 | None | None | I |
| N/T | 0.3467 | ambiguous | 0.2634 | benign | -0.112 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | N | 0.501278926 | None | None | I |
| N/V | 0.6155 | likely_pathogenic | 0.5248 | ambiguous | -0.06 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | I |
| N/W | 0.842 | likely_pathogenic | 0.8399 | pathogenic | -0.596 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| N/Y | 0.266 | likely_benign | 0.2392 | benign | -0.337 | Destabilizing | 1.0 | D | 0.657 | neutral | D | 0.618230155 | 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.