Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15753 | 47482;47483;47484 | chr2:178618201;178618200;178618199 | chr2:179482928;179482927;179482926 |
| N2AB | 14112 | 42559;42560;42561 | chr2:178618201;178618200;178618199 | chr2:179482928;179482927;179482926 |
| N2A | 13185 | 39778;39779;39780 | chr2:178618201;178618200;178618199 | chr2:179482928;179482927;179482926 |
| N2B | 6688 | 20287;20288;20289 | chr2:178618201;178618200;178618199 | chr2:179482928;179482927;179482926 |
| Novex-1 | 6813 | 20662;20663;20664 | chr2:178618201;178618200;178618199 | chr2:179482928;179482927;179482926 |
| Novex-2 | 6880 | 20863;20864;20865 | chr2:178618201;178618200;178618199 | chr2:179482928;179482927;179482926 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs577133803  |
-0.468 | None | N | 0.135 | 0.096 | 0.202086224978 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| R/K | rs577133803 |
-0.468 | None | N | 0.135 | 0.096 | 0.202086224978 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 0 |
| R/K | rs577133803 |
-0.468 | None | N | 0.135 | 0.096 | 0.202086224978 | gnomAD-4.0.0 | 6.82291E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.3294E-06 | 0 | 0 |
| R/T | None | None | 0.361 | N | 0.482 | 0.14 | 0.271763555656 | gnomAD-4.0.0 | 6.84768E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99952E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3804 | ambiguous | 0.3595 | ambiguous | -0.313 | Destabilizing | 0.134 | N | 0.425 | neutral | None | None | None | None | N |
| R/C | 0.2041 | likely_benign | 0.1776 | benign | -0.223 | Destabilizing | 0.984 | D | 0.56 | neutral | None | None | None | None | N |
| R/D | 0.7486 | likely_pathogenic | 0.7176 | pathogenic | -0.027 | Destabilizing | 0.428 | N | 0.468 | neutral | None | None | None | None | N |
| R/E | 0.3953 | ambiguous | 0.3757 | ambiguous | 0.036 | Stabilizing | 0.134 | N | 0.419 | neutral | None | None | None | None | N |
| R/F | 0.5553 | ambiguous | 0.5135 | ambiguous | -0.508 | Destabilizing | 0.942 | D | 0.529 | neutral | None | None | None | None | N |
| R/G | 0.3128 | likely_benign | 0.3095 | benign | -0.532 | Destabilizing | 0.361 | N | 0.379 | neutral | N | 0.458491107 | None | None | N |
| R/H | 0.1292 | likely_benign | 0.113 | benign | -0.972 | Destabilizing | 0.842 | D | 0.387 | neutral | None | None | None | None | N |
| R/I | 0.255 | likely_benign | 0.2341 | benign | 0.237 | Stabilizing | 0.842 | D | 0.565 | neutral | None | None | None | None | N |
| R/K | 0.0775 | likely_benign | 0.0708 | benign | -0.259 | Destabilizing | None | N | 0.135 | neutral | N | 0.348065521 | None | None | N |
| R/L | 0.2584 | likely_benign | 0.2497 | benign | 0.237 | Stabilizing | 0.428 | N | 0.379 | neutral | None | None | None | None | N |
| R/M | 0.3026 | likely_benign | 0.2762 | benign | 0.025 | Stabilizing | 0.924 | D | 0.424 | neutral | N | 0.474373844 | None | None | N |
| R/N | 0.5983 | likely_pathogenic | 0.5402 | ambiguous | 0.237 | Stabilizing | 0.428 | N | 0.469 | neutral | None | None | None | None | N |
| R/P | 0.8479 | likely_pathogenic | 0.8893 | pathogenic | 0.074 | Stabilizing | 0.842 | D | 0.511 | neutral | None | None | None | None | N |
| R/Q | 0.1143 | likely_benign | 0.1077 | benign | -0.005 | Destabilizing | 0.272 | N | 0.545 | neutral | None | None | None | None | N |
| R/S | 0.4957 | ambiguous | 0.4605 | ambiguous | -0.325 | Destabilizing | 0.22 | N | 0.439 | neutral | N | 0.459962771 | None | None | N |
| R/T | 0.2493 | likely_benign | 0.2211 | benign | -0.121 | Destabilizing | 0.361 | N | 0.482 | neutral | N | 0.450868781 | None | None | N |
| R/V | 0.2888 | likely_benign | 0.2577 | benign | 0.074 | Stabilizing | 0.724 | D | 0.479 | neutral | None | None | None | None | N |
| R/W | 0.2719 | likely_benign | 0.2577 | benign | -0.397 | Destabilizing | 0.979 | D | 0.659 | prob.neutral | N | 0.471235555 | None | None | N |
| R/Y | 0.4591 | ambiguous | 0.4171 | ambiguous | -0.017 | Destabilizing | 0.942 | D | 0.561 | 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.