Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22460 | 67603;67604;67605 | chr2:178579819;178579818;178579817 | chr2:179444546;179444545;179444544 |
| N2AB | 20819 | 62680;62681;62682 | chr2:178579819;178579818;178579817 | chr2:179444546;179444545;179444544 |
| N2A | 19892 | 59899;59900;59901 | chr2:178579819;178579818;178579817 | chr2:179444546;179444545;179444544 |
| N2B | 13395 | 40408;40409;40410 | chr2:178579819;178579818;178579817 | chr2:179444546;179444545;179444544 |
| Novex-1 | 13520 | 40783;40784;40785 | chr2:178579819;178579818;178579817 | chr2:179444546;179444545;179444544 |
| Novex-2 | 13587 | 40984;40985;40986 | chr2:178579819;178579818;178579817 | chr2:179444546;179444545;179444544 |
| 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/G | None | None | 0.012 | N | 0.466 | 0.283 | 0.522344865107 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| V/L | rs769408902  |
-0.25 | 0.012 | N | 0.391 | 0.131 | 0.346768085243 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| V/L | rs769408902 |
-0.25 | 0.012 | N | 0.391 | 0.131 | 0.346768085243 | gnomAD-4.0.0 | 1.36882E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.31444E-05 |
| V/M | rs769408902 |
None | 0.295 | N | 0.582 | 0.213 | 0.39709148275 | gnomAD-4.0.0 | 6.84411E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99675E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1578 | likely_benign | 0.1231 | benign | -1.005 | Destabilizing | None | N | 0.133 | neutral | N | 0.48329158 | None | None | N |
| V/C | 0.7085 | likely_pathogenic | 0.6382 | pathogenic | -0.89 | Destabilizing | 0.356 | N | 0.635 | neutral | None | None | None | None | N |
| V/D | 0.5659 | likely_pathogenic | 0.4758 | ambiguous | -0.405 | Destabilizing | 0.072 | N | 0.706 | prob.neutral | None | None | None | None | N |
| V/E | 0.4127 | ambiguous | 0.3381 | benign | -0.41 | Destabilizing | 0.055 | N | 0.556 | neutral | N | 0.493874948 | None | None | N |
| V/F | 0.3072 | likely_benign | 0.2696 | benign | -0.672 | Destabilizing | 0.356 | N | 0.675 | prob.neutral | None | None | None | None | N |
| V/G | 0.2524 | likely_benign | 0.2024 | benign | -1.3 | Destabilizing | 0.012 | N | 0.466 | neutral | N | 0.49286099 | None | None | N |
| V/H | 0.7417 | likely_pathogenic | 0.6659 | pathogenic | -0.71 | Destabilizing | 0.628 | D | 0.69 | prob.neutral | None | None | None | None | N |
| V/I | 0.095 | likely_benign | 0.094 | benign | -0.317 | Destabilizing | 0.031 | N | 0.508 | neutral | None | None | None | None | N |
| V/K | 0.5075 | ambiguous | 0.4107 | ambiguous | -0.86 | Destabilizing | 0.072 | N | 0.581 | neutral | None | None | None | None | N |
| V/L | 0.2385 | likely_benign | 0.2002 | benign | -0.317 | Destabilizing | 0.012 | N | 0.391 | neutral | N | 0.49489544 | None | None | N |
| V/M | 0.2132 | likely_benign | 0.1839 | benign | -0.42 | Destabilizing | 0.295 | N | 0.582 | neutral | N | 0.48611304 | None | None | N |
| V/N | 0.448 | ambiguous | 0.3579 | ambiguous | -0.688 | Destabilizing | 0.072 | N | 0.726 | prob.delet. | None | None | None | None | N |
| V/P | 0.232 | likely_benign | 0.1986 | benign | -0.509 | Destabilizing | 0.072 | N | 0.672 | neutral | None | None | None | None | N |
| V/Q | 0.4517 | ambiguous | 0.378 | ambiguous | -0.792 | Destabilizing | 0.356 | N | 0.689 | prob.neutral | None | None | None | None | N |
| V/R | 0.4823 | ambiguous | 0.3958 | ambiguous | -0.421 | Destabilizing | 0.214 | N | 0.732 | prob.delet. | None | None | None | None | N |
| V/S | 0.301 | likely_benign | 0.2269 | benign | -1.254 | Destabilizing | 0.001 | N | 0.372 | neutral | None | None | None | None | N |
| V/T | 0.2654 | likely_benign | 0.2079 | benign | -1.132 | Destabilizing | 0.016 | N | 0.459 | neutral | None | None | None | None | N |
| V/W | 0.8633 | likely_pathogenic | 0.8366 | pathogenic | -0.816 | Destabilizing | 0.864 | D | 0.679 | prob.neutral | None | None | None | None | N |
| V/Y | 0.6348 | likely_pathogenic | 0.5607 | ambiguous | -0.519 | Destabilizing | 0.356 | N | 0.645 | 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.