Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32360 | 97303;97304;97305 | chr2:178542776;178542775;178542774 | chr2:179407503;179407502;179407501 |
| N2AB | 30719 | 92380;92381;92382 | chr2:178542776;178542775;178542774 | chr2:179407503;179407502;179407501 |
| N2A | 29792 | 89599;89600;89601 | chr2:178542776;178542775;178542774 | chr2:179407503;179407502;179407501 |
| N2B | 23295 | 70108;70109;70110 | chr2:178542776;178542775;178542774 | chr2:179407503;179407502;179407501 |
| Novex-1 | 23420 | 70483;70484;70485 | chr2:178542776;178542775;178542774 | chr2:179407503;179407502;179407501 |
| Novex-2 | 23487 | 70684;70685;70686 | chr2:178542776;178542775;178542774 | chr2:179407503;179407502;179407501 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | None | None | 0.996 | N | 0.625 | 0.44 | 0.376921832658 | gnomAD-4.0.0 | 6.842E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99467E-07 | 0 | 0 |
| K/Q | rs751750046  |
0.313 | 0.999 | N | 0.716 | 0.331 | 0.277730125212 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| K/Q | rs751750046 |
0.313 | 0.999 | N | 0.716 | 0.331 | 0.277730125212 | gnomAD-4.0.0 | 2.0526E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.46861E-04 | 8.99467E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.2307 | likely_benign | 0.2083 | benign | 0.016 | Stabilizing | 0.998 | D | 0.672 | neutral | None | None | None | None | N |
| K/C | 0.6794 | likely_pathogenic | 0.6435 | pathogenic | -0.361 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| K/D | 0.3335 | likely_benign | 0.3081 | benign | 0.017 | Stabilizing | 0.998 | D | 0.67 | neutral | None | None | None | None | N |
| K/E | 0.1605 | likely_benign | 0.139 | benign | 0.043 | Stabilizing | 0.996 | D | 0.625 | neutral | N | 0.45886843 | None | None | N |
| K/F | 0.7946 | likely_pathogenic | 0.7578 | pathogenic | -0.093 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| K/G | 0.2517 | likely_benign | 0.2309 | benign | -0.203 | Destabilizing | 0.997 | D | 0.655 | neutral | None | None | None | None | N |
| K/H | 0.2897 | likely_benign | 0.2697 | benign | -0.379 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| K/I | 0.4549 | ambiguous | 0.4169 | ambiguous | 0.519 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.491655639 | None | None | N |
| K/L | 0.398 | ambiguous | 0.3556 | ambiguous | 0.519 | Stabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| K/M | 0.2505 | likely_benign | 0.2259 | benign | 0.129 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| K/N | 0.2677 | likely_benign | 0.2398 | benign | 0.009 | Stabilizing | 0.884 | D | 0.355 | neutral | N | 0.441533463 | None | None | N |
| K/P | 0.5602 | ambiguous | 0.5316 | ambiguous | 0.38 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| K/Q | 0.132 | likely_benign | 0.1221 | benign | -0.103 | Destabilizing | 0.999 | D | 0.716 | prob.delet. | N | 0.498080179 | None | None | N |
| K/R | 0.0797 | likely_benign | 0.0783 | benign | -0.135 | Destabilizing | 0.998 | D | 0.591 | neutral | N | 0.484862952 | None | None | N |
| K/S | 0.2769 | likely_benign | 0.2424 | benign | -0.448 | Destabilizing | 0.997 | D | 0.651 | neutral | None | None | None | None | N |
| K/T | 0.1397 | likely_benign | 0.1301 | benign | -0.268 | Destabilizing | 0.999 | D | 0.669 | neutral | N | 0.470317574 | None | None | N |
| K/V | 0.3518 | ambiguous | 0.3214 | benign | 0.38 | Stabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| K/W | 0.7494 | likely_pathogenic | 0.7261 | pathogenic | -0.127 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| K/Y | 0.6023 | likely_pathogenic | 0.5656 | pathogenic | 0.214 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | 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.