Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22501 | 67726;67727;67728 | chr2:178579696;178579695;178579694 | chr2:179444423;179444422;179444421 |
| N2AB | 20860 | 62803;62804;62805 | chr2:178579696;178579695;178579694 | chr2:179444423;179444422;179444421 |
| N2A | 19933 | 60022;60023;60024 | chr2:178579696;178579695;178579694 | chr2:179444423;179444422;179444421 |
| N2B | 13436 | 40531;40532;40533 | chr2:178579696;178579695;178579694 | chr2:179444423;179444422;179444421 |
| Novex-1 | 13561 | 40906;40907;40908 | chr2:178579696;178579695;178579694 | chr2:179444423;179444422;179444421 |
| Novex-2 | 13628 | 41107;41108;41109 | chr2:178579696;178579695;178579694 | chr2:179444423;179444422;179444421 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs751903421  |
-0.139 | 0.955 | N | 0.399 | 0.233 | 0.498323335527 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| M/I | rs751903421 |
-0.139 | 0.955 | N | 0.399 | 0.233 | 0.498323335527 | gnomAD-4.0.0 | 1.77943E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.33913E-05 | 0 | 0 |
| M/L | None | None | 0.651 | N | 0.255 | 0.171 | 0.538745750885 | gnomAD-4.0.0 | 1.59229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.7787E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs2047253613 |
None | 0.912 | N | 0.456 | 0.204 | 0.736034458054 | gnomAD-4.0.0 | 2.73757E-06 | None | None | None | None | N | None | 2.98989E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69897E-06 | 0 | 0 |
| M/V | None | None | 0.81 | N | 0.435 | 0.186 | 0.445614145163 | gnomAD-4.0.0 | 1.59229E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.351 | ambiguous | 0.3213 | benign | -1.793 | Destabilizing | 0.072 | N | 0.21 | neutral | None | None | None | None | N |
| M/C | 0.6535 | likely_pathogenic | 0.6103 | pathogenic | -1.57 | Destabilizing | 0.999 | D | 0.498 | neutral | None | None | None | None | N |
| M/D | 0.814 | likely_pathogenic | 0.823 | pathogenic | -0.586 | Destabilizing | 0.965 | D | 0.534 | neutral | None | None | None | None | N |
| M/E | 0.5362 | ambiguous | 0.5538 | ambiguous | -0.468 | Destabilizing | 0.932 | D | 0.481 | neutral | None | None | None | None | N |
| M/F | 0.3603 | ambiguous | 0.3677 | ambiguous | -0.498 | Destabilizing | 0.99 | D | 0.495 | neutral | None | None | None | None | N |
| M/G | 0.4618 | ambiguous | 0.4255 | ambiguous | -2.195 | Highly Destabilizing | 0.932 | D | 0.514 | neutral | None | None | None | None | N |
| M/H | 0.5316 | ambiguous | 0.5068 | ambiguous | -1.315 | Destabilizing | 0.041 | N | 0.361 | neutral | None | None | None | None | N |
| M/I | 0.5346 | ambiguous | 0.5427 | ambiguous | -0.71 | Destabilizing | 0.955 | D | 0.399 | neutral | N | 0.445482553 | None | None | N |
| M/K | 0.23 | likely_benign | 0.2497 | benign | -0.722 | Destabilizing | 0.122 | N | 0.243 | neutral | N | 0.422509693 | None | None | N |
| M/L | 0.1445 | likely_benign | 0.1644 | benign | -0.71 | Destabilizing | 0.651 | D | 0.255 | neutral | N | 0.415565078 | None | None | N |
| M/N | 0.4702 | ambiguous | 0.4721 | ambiguous | -0.812 | Destabilizing | 0.932 | D | 0.517 | neutral | None | None | None | None | N |
| M/P | 0.9549 | likely_pathogenic | 0.9611 | pathogenic | -1.045 | Destabilizing | 0.997 | D | 0.558 | neutral | None | None | None | None | N |
| M/Q | 0.2351 | likely_benign | 0.216 | benign | -0.708 | Destabilizing | 0.932 | D | 0.449 | neutral | None | None | None | None | N |
| M/R | 0.2557 | likely_benign | 0.2865 | benign | -0.456 | Destabilizing | 0.838 | D | 0.453 | neutral | N | 0.455102114 | None | None | N |
| M/S | 0.3548 | ambiguous | 0.3265 | benign | -1.49 | Destabilizing | 0.739 | D | 0.455 | neutral | None | None | None | None | N |
| M/T | 0.2353 | likely_benign | 0.2227 | benign | -1.242 | Destabilizing | 0.912 | D | 0.456 | neutral | N | 0.386490178 | None | None | N |
| M/V | 0.156 | likely_benign | 0.1628 | benign | -1.045 | Destabilizing | 0.81 | D | 0.435 | neutral | N | 0.42939838 | None | None | N |
| M/W | 0.68 | likely_pathogenic | 0.7255 | pathogenic | -0.553 | Destabilizing | 0.999 | D | 0.508 | neutral | None | None | None | None | N |
| M/Y | 0.6165 | likely_pathogenic | 0.6206 | pathogenic | -0.556 | Destabilizing | 0.98 | D | 0.545 | 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.