Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21472 | 64639;64640;64641 | chr2:178585330;178585329;178585328 | chr2:179450057;179450056;179450055 |
| N2AB | 19831 | 59716;59717;59718 | chr2:178585330;178585329;178585328 | chr2:179450057;179450056;179450055 |
| N2A | 18904 | 56935;56936;56937 | chr2:178585330;178585329;178585328 | chr2:179450057;179450056;179450055 |
| N2B | 12407 | 37444;37445;37446 | chr2:178585330;178585329;178585328 | chr2:179450057;179450056;179450055 |
| Novex-1 | 12532 | 37819;37820;37821 | chr2:178585330;178585329;178585328 | chr2:179450057;179450056;179450055 |
| Novex-2 | 12599 | 38020;38021;38022 | chr2:178585330;178585329;178585328 | chr2:179450057;179450056;179450055 |
| 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 | rs2048686621  |
None | 0.027 | N | 0.458 | 0.184 | 0.368183359018 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs2048686621 |
None | 0.027 | N | 0.458 | 0.184 | 0.368183359018 | gnomAD-4.0.0 | 6.57903E-06 | None | None | None | None | N | None | 0 | 6.55824E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | None | None | None | N | 0.214 | 0.132 | 0.253205268125 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| M/T | rs372682546 |
-0.898 | 0.117 | N | 0.516 | 0.261 | None | gnomAD-2.1.1 | 4.3E-06 | None | None | None | None | N | None | 6.59E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs372682546 |
-0.898 | 0.117 | N | 0.516 | 0.261 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs372682546 |
-0.898 | 0.117 | N | 0.516 | 0.261 | None | gnomAD-4.0.0 | 5.27016E-06 | None | None | None | None | N | None | 3.46141E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.88696E-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 | 0.8007 | likely_pathogenic | 0.8134 | pathogenic | -2.455 | Highly Destabilizing | 0.067 | N | 0.481 | neutral | None | None | None | None | N |
| M/C | 0.8257 | likely_pathogenic | 0.8584 | pathogenic | -1.95 | Destabilizing | 0.935 | D | 0.562 | neutral | None | None | None | None | N |
| M/D | 0.9952 | likely_pathogenic | 0.9942 | pathogenic | -1.499 | Destabilizing | 0.791 | D | 0.627 | neutral | None | None | None | None | N |
| M/E | 0.9738 | likely_pathogenic | 0.9675 | pathogenic | -1.36 | Destabilizing | 0.555 | D | 0.592 | neutral | None | None | None | None | N |
| M/F | 0.4786 | ambiguous | 0.4912 | ambiguous | -1.008 | Destabilizing | 0.081 | N | 0.557 | neutral | None | None | None | None | N |
| M/G | 0.9276 | likely_pathogenic | 0.9325 | pathogenic | -2.879 | Highly Destabilizing | 0.262 | N | 0.57 | neutral | None | None | None | None | N |
| M/H | 0.9398 | likely_pathogenic | 0.9321 | pathogenic | -2.09 | Highly Destabilizing | 0.935 | D | 0.602 | neutral | None | None | None | None | N |
| M/I | 0.6023 | likely_pathogenic | 0.5922 | pathogenic | -1.276 | Destabilizing | 0.027 | N | 0.458 | neutral | N | 0.448703711 | None | None | N |
| M/K | 0.8834 | likely_pathogenic | 0.8422 | pathogenic | -1.401 | Destabilizing | 0.211 | N | 0.53 | neutral | N | 0.494742645 | None | None | N |
| M/L | 0.1316 | likely_benign | 0.1325 | benign | -1.276 | Destabilizing | None | N | 0.214 | neutral | N | 0.428173724 | None | None | N |
| M/N | 0.9572 | likely_pathogenic | 0.9549 | pathogenic | -1.462 | Destabilizing | 0.791 | D | 0.613 | neutral | None | None | None | None | N |
| M/P | 0.9806 | likely_pathogenic | 0.9773 | pathogenic | -1.647 | Destabilizing | 0.791 | D | 0.604 | neutral | None | None | None | None | N |
| M/Q | 0.8284 | likely_pathogenic | 0.794 | pathogenic | -1.356 | Destabilizing | 0.791 | D | 0.587 | neutral | None | None | None | None | N |
| M/R | 0.9033 | likely_pathogenic | 0.87 | pathogenic | -1.1 | Destabilizing | 0.484 | N | 0.576 | neutral | N | 0.495956154 | None | None | N |
| M/S | 0.8758 | likely_pathogenic | 0.8852 | pathogenic | -2.12 | Highly Destabilizing | 0.262 | N | 0.499 | neutral | None | None | None | None | N |
| M/T | 0.7387 | likely_pathogenic | 0.7535 | pathogenic | -1.862 | Destabilizing | 0.117 | N | 0.516 | neutral | N | 0.477370393 | None | None | N |
| M/V | 0.229 | likely_benign | 0.2331 | benign | -1.647 | Destabilizing | 0.001 | N | 0.241 | neutral | N | 0.47771711 | None | None | N |
| M/W | 0.9279 | likely_pathogenic | 0.9145 | pathogenic | -1.098 | Destabilizing | 0.935 | D | 0.559 | neutral | None | None | None | None | N |
| M/Y | 0.8952 | likely_pathogenic | 0.8869 | pathogenic | -1.175 | Destabilizing | 0.555 | D | 0.583 | 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.