Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21578 | 64957;64958;64959 | chr2:178584909;178584908;178584907 | chr2:179449636;179449635;179449634 |
| N2AB | 19937 | 60034;60035;60036 | chr2:178584909;178584908;178584907 | chr2:179449636;179449635;179449634 |
| N2A | 19010 | 57253;57254;57255 | chr2:178584909;178584908;178584907 | chr2:179449636;179449635;179449634 |
| N2B | 12513 | 37762;37763;37764 | chr2:178584909;178584908;178584907 | chr2:179449636;179449635;179449634 |
| Novex-1 | 12638 | 38137;38138;38139 | chr2:178584909;178584908;178584907 | chr2:179449636;179449635;179449634 |
| Novex-2 | 12705 | 38338;38339;38340 | chr2:178584909;178584908;178584907 | chr2:179449636;179449635;179449634 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | None | None | 0.883 | N | 0.611 | 0.246 | 0.371344866733 | gnomAD-4.0.0 | 1.59234E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41663E-04 | 0 | 0 | 0 |
| S/P | None | None | 0.667 | N | 0.568 | 0.271 | 0.186928172975 | gnomAD-4.0.0 | 1.59231E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85997E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1004 | likely_benign | 0.0997 | benign | -0.491 | Destabilizing | 0.055 | N | 0.389 | neutral | N | 0.458241206 | None | None | N |
| S/C | 0.0884 | likely_benign | 0.0922 | benign | -0.68 | Destabilizing | 0.883 | D | 0.611 | neutral | N | 0.491065701 | None | None | N |
| S/D | 0.6448 | likely_pathogenic | 0.6598 | pathogenic | -1.422 | Destabilizing | 0.272 | N | 0.437 | neutral | None | None | None | None | N |
| S/E | 0.705 | likely_pathogenic | 0.7178 | pathogenic | -1.409 | Destabilizing | 0.272 | N | 0.43 | neutral | None | None | None | None | N |
| S/F | 0.181 | likely_benign | 0.1829 | benign | -0.901 | Destabilizing | 0.667 | D | 0.687 | prob.neutral | N | 0.498261032 | None | None | N |
| S/G | 0.1562 | likely_benign | 0.1625 | benign | -0.714 | Destabilizing | 0.272 | N | 0.444 | neutral | None | None | None | None | N |
| S/H | 0.3324 | likely_benign | 0.3561 | ambiguous | -1.298 | Destabilizing | 0.968 | D | 0.605 | neutral | None | None | None | None | N |
| S/I | 0.1238 | likely_benign | 0.1273 | benign | -0.006 | Destabilizing | 0.396 | N | 0.625 | neutral | None | None | None | None | N |
| S/K | 0.7861 | likely_pathogenic | 0.8005 | pathogenic | -0.666 | Destabilizing | 0.272 | N | 0.435 | neutral | None | None | None | None | N |
| S/L | 0.087 | likely_benign | 0.0879 | benign | -0.006 | Destabilizing | 0.157 | N | 0.544 | neutral | None | None | None | None | N |
| S/M | 0.155 | likely_benign | 0.1534 | benign | 0.334 | Stabilizing | 0.909 | D | 0.607 | neutral | None | None | None | None | N |
| S/N | 0.1706 | likely_benign | 0.1739 | benign | -0.937 | Destabilizing | 0.272 | N | 0.443 | neutral | None | None | None | None | N |
| S/P | 0.8448 | likely_pathogenic | 0.8664 | pathogenic | -0.136 | Destabilizing | 0.667 | D | 0.568 | neutral | N | 0.475789784 | None | None | N |
| S/Q | 0.5518 | ambiguous | 0.5725 | pathogenic | -1.185 | Destabilizing | 0.726 | D | 0.525 | neutral | None | None | None | None | N |
| S/R | 0.7095 | likely_pathogenic | 0.7351 | pathogenic | -0.489 | Destabilizing | 0.567 | D | 0.565 | neutral | None | None | None | None | N |
| S/T | 0.0592 | likely_benign | 0.0612 | benign | -0.753 | Destabilizing | None | N | 0.255 | neutral | N | 0.346089137 | None | None | N |
| S/V | 0.1321 | likely_benign | 0.1334 | benign | -0.136 | Destabilizing | 0.157 | N | 0.539 | neutral | None | None | None | None | N |
| S/W | 0.3557 | ambiguous | 0.3914 | ambiguous | -0.987 | Destabilizing | 0.968 | D | 0.759 | deleterious | None | None | None | None | N |
| S/Y | 0.1822 | likely_benign | 0.1882 | benign | -0.614 | Destabilizing | 0.667 | D | 0.689 | prob.neutral | N | 0.488564113 | 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.