Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16674 | 50245;50246;50247 | chr2:178612505;178612504;178612503 | chr2:179477232;179477231;179477230 |
| N2AB | 15033 | 45322;45323;45324 | chr2:178612505;178612504;178612503 | chr2:179477232;179477231;179477230 |
| N2A | 14106 | 42541;42542;42543 | chr2:178612505;178612504;178612503 | chr2:179477232;179477231;179477230 |
| N2B | 7609 | 23050;23051;23052 | chr2:178612505;178612504;178612503 | chr2:179477232;179477231;179477230 |
| Novex-1 | 7734 | 23425;23426;23427 | chr2:178612505;178612504;178612503 | chr2:179477232;179477231;179477230 |
| Novex-2 | 7801 | 23626;23627;23628 | chr2:178612505;178612504;178612503 | chr2:179477232;179477231;179477230 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs2056518372  |
None | 0.454 | N | 0.457 | 0.141 | 0.37568098594 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs2056518372 |
None | 0.454 | N | 0.457 | 0.141 | 0.37568098594 | gnomAD-4.0.0 | 5.58331E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.63272E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1437 | likely_benign | 0.1762 | benign | -1.641 | Destabilizing | 0.005 | N | 0.109 | neutral | N | 0.376751143 | None | None | N |
| V/C | 0.8161 | likely_pathogenic | 0.8221 | pathogenic | -1.165 | Destabilizing | 0.998 | D | 0.579 | neutral | None | None | None | None | N |
| V/D | 0.3939 | ambiguous | 0.618 | pathogenic | -1.537 | Destabilizing | 0.669 | D | 0.58 | neutral | N | 0.478681547 | None | None | N |
| V/E | 0.2518 | likely_benign | 0.41 | ambiguous | -1.465 | Destabilizing | 0.067 | N | 0.425 | neutral | None | None | None | None | N |
| V/F | 0.2241 | likely_benign | 0.2916 | benign | -1.115 | Destabilizing | 0.934 | D | 0.593 | neutral | N | 0.473207754 | None | None | N |
| V/G | 0.2962 | likely_benign | 0.3995 | ambiguous | -2.027 | Highly Destabilizing | 0.669 | D | 0.521 | neutral | N | 0.468027107 | None | None | N |
| V/H | 0.6238 | likely_pathogenic | 0.7391 | pathogenic | -1.436 | Destabilizing | 0.998 | D | 0.599 | neutral | None | None | None | None | N |
| V/I | 0.0845 | likely_benign | 0.0804 | benign | -0.65 | Destabilizing | 0.454 | N | 0.457 | neutral | N | 0.480874488 | None | None | N |
| V/K | 0.306 | likely_benign | 0.5301 | ambiguous | -1.449 | Destabilizing | 0.842 | D | 0.532 | neutral | None | None | None | None | N |
| V/L | 0.1813 | likely_benign | 0.202 | benign | -0.65 | Destabilizing | 0.012 | N | 0.14 | neutral | N | 0.47559197 | None | None | N |
| V/M | 0.1644 | likely_benign | 0.1733 | benign | -0.561 | Destabilizing | 0.949 | D | 0.515 | neutral | None | None | None | None | N |
| V/N | 0.3075 | likely_benign | 0.4137 | ambiguous | -1.41 | Destabilizing | 0.974 | D | 0.621 | neutral | None | None | None | None | N |
| V/P | 0.2513 | likely_benign | 0.3413 | ambiguous | -0.946 | Destabilizing | 0.974 | D | 0.613 | neutral | None | None | None | None | N |
| V/Q | 0.3067 | likely_benign | 0.4248 | ambiguous | -1.471 | Destabilizing | 0.949 | D | 0.611 | neutral | None | None | None | None | N |
| V/R | 0.3293 | likely_benign | 0.5595 | ambiguous | -0.969 | Destabilizing | 0.949 | D | 0.62 | neutral | None | None | None | None | N |
| V/S | 0.2089 | likely_benign | 0.27 | benign | -1.978 | Destabilizing | 0.728 | D | 0.499 | neutral | None | None | None | None | N |
| V/T | 0.1849 | likely_benign | 0.2111 | benign | -1.775 | Destabilizing | 0.842 | D | 0.433 | neutral | None | None | None | None | N |
| V/W | 0.8783 | likely_pathogenic | 0.9304 | pathogenic | -1.36 | Destabilizing | 0.998 | D | 0.649 | neutral | None | None | None | None | N |
| V/Y | 0.6151 | likely_pathogenic | 0.7377 | pathogenic | -1.048 | Destabilizing | 0.991 | D | 0.599 | 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.