Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14112 | 42559;42560;42561 | chr2:178634447;178634446;178634445 | chr2:179499174;179499173;179499172 |
| N2AB | 12471 | 37636;37637;37638 | chr2:178634447;178634446;178634445 | chr2:179499174;179499173;179499172 |
| N2A | 11544 | 34855;34856;34857 | chr2:178634447;178634446;178634445 | chr2:179499174;179499173;179499172 |
| N2B | 5047 | 15364;15365;15366 | chr2:178634447;178634446;178634445 | chr2:179499174;179499173;179499172 |
| Novex-1 | 5172 | 15739;15740;15741 | chr2:178634447;178634446;178634445 | chr2:179499174;179499173;179499172 |
| Novex-2 | 5239 | 15940;15941;15942 | chr2:178634447;178634446;178634445 | chr2:179499174;179499173;179499172 |
| 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/I | rs749717066  |
0.25 | 0.056 | D | 0.481 | 0.34 | 0.486494567076 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| N/S | rs749717066 |
-0.947 | 0.944 | N | 0.419 | 0.329 | 0.28297238246 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| N/S | rs749717066 |
-0.947 | 0.944 | N | 0.419 | 0.329 | 0.28297238246 | gnomAD-4.0.0 | 6.00162E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56252E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.5349 | ambiguous | 0.4966 | ambiguous | -0.756 | Destabilizing | 0.916 | D | 0.577 | neutral | None | None | None | None | N |
| N/C | 0.5527 | ambiguous | 0.5061 | ambiguous | -0.07 | Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | N |
| N/D | 0.417 | ambiguous | 0.3744 | ambiguous | -1.144 | Destabilizing | 0.981 | D | 0.463 | neutral | N | 0.507617607 | None | None | N |
| N/E | 0.7154 | likely_pathogenic | 0.6677 | pathogenic | -1.051 | Destabilizing | 0.996 | D | 0.619 | neutral | None | None | None | None | N |
| N/F | 0.8235 | likely_pathogenic | 0.7857 | pathogenic | -0.694 | Destabilizing | 0.975 | D | 0.791 | deleterious | None | None | None | None | N |
| N/G | 0.5184 | ambiguous | 0.5008 | ambiguous | -1.078 | Destabilizing | 0.957 | D | 0.419 | neutral | None | None | None | None | N |
| N/H | 0.1534 | likely_benign | 0.1354 | benign | -0.935 | Destabilizing | 0.994 | D | 0.675 | neutral | N | 0.496934455 | None | None | N |
| N/I | 0.5812 | likely_pathogenic | 0.5272 | ambiguous | 0.055 | Stabilizing | 0.056 | N | 0.481 | neutral | D | 0.545689118 | None | None | N |
| N/K | 0.5192 | ambiguous | 0.4547 | ambiguous | -0.202 | Destabilizing | 0.983 | D | 0.617 | neutral | N | 0.467679001 | None | None | N |
| N/L | 0.4683 | ambiguous | 0.4429 | ambiguous | 0.055 | Stabilizing | 0.653 | D | 0.594 | neutral | None | None | None | None | N |
| N/M | 0.6662 | likely_pathogenic | 0.6428 | pathogenic | 0.614 | Stabilizing | 0.993 | D | 0.752 | deleterious | None | None | None | None | N |
| N/P | 0.8058 | likely_pathogenic | 0.8432 | pathogenic | -0.186 | Destabilizing | 0.996 | D | 0.773 | deleterious | None | None | None | None | N |
| N/Q | 0.568 | likely_pathogenic | 0.524 | ambiguous | -1.008 | Destabilizing | 0.996 | D | 0.705 | prob.neutral | None | None | None | None | N |
| N/R | 0.4744 | ambiguous | 0.38 | ambiguous | -0.17 | Destabilizing | 0.996 | D | 0.698 | prob.neutral | None | None | None | None | N |
| N/S | 0.134 | likely_benign | 0.1273 | benign | -0.872 | Destabilizing | 0.944 | D | 0.419 | neutral | N | 0.499181929 | None | None | N |
| N/T | 0.3041 | likely_benign | 0.2685 | benign | -0.599 | Destabilizing | 0.892 | D | 0.497 | neutral | N | 0.509509492 | None | None | N |
| N/V | 0.6132 | likely_pathogenic | 0.5624 | ambiguous | -0.186 | Destabilizing | 0.653 | D | 0.609 | neutral | None | None | None | None | N |
| N/W | 0.8879 | likely_pathogenic | 0.8604 | pathogenic | -0.51 | Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | N |
| N/Y | 0.3384 | likely_benign | 0.278 | benign | -0.233 | Destabilizing | 0.983 | D | 0.777 | deleterious | N | 0.508628001 | 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.