Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23606 | 71041;71042;71043 | chr2:178575316;178575315;178575314 | chr2:179440043;179440042;179440041 |
| N2AB | 21965 | 66118;66119;66120 | chr2:178575316;178575315;178575314 | chr2:179440043;179440042;179440041 |
| N2A | 21038 | 63337;63338;63339 | chr2:178575316;178575315;178575314 | chr2:179440043;179440042;179440041 |
| N2B | 14541 | 43846;43847;43848 | chr2:178575316;178575315;178575314 | chr2:179440043;179440042;179440041 |
| Novex-1 | 14666 | 44221;44222;44223 | chr2:178575316;178575315;178575314 | chr2:179440043;179440042;179440041 |
| Novex-2 | 14733 | 44422;44423;44424 | chr2:178575316;178575315;178575314 | chr2:179440043;179440042;179440041 |
| 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/T | rs371030086  |
-2.064 | 0.684 | N | 0.688 | 0.303 | None | gnomAD-2.1.1 | 5E-05 | None | None | None | None | N | None | 4.96032E-04 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs371030086 |
-2.064 | 0.684 | N | 0.688 | 0.303 | None | gnomAD-3.1.2 | 2.23508E-04 | None | None | None | None | N | None | 7.4825E-04 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 9.56938E-04 |
| M/T | rs371030086 |
-2.064 | 0.684 | N | 0.688 | 0.303 | None | gnomAD-4.0.0 | 3.59464E-05 | None | None | None | None | N | None | 6.53194E-04 | 4.9995E-05 | None | 0 | 0 | None | 0 | 1.65125E-04 | 0 | 0 | 8.00384E-05 |
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 | 0.5158 | ambiguous | 0.5629 | ambiguous | -2.379 | Highly Destabilizing | 0.373 | N | 0.645 | neutral | None | None | None | None | N |
| M/C | 0.7108 | likely_pathogenic | 0.7176 | pathogenic | -2.414 | Highly Destabilizing | 0.996 | D | 0.655 | neutral | None | None | None | None | N |
| M/D | 0.9725 | likely_pathogenic | 0.9751 | pathogenic | -2.46 | Highly Destabilizing | 0.91 | D | 0.695 | prob.neutral | None | None | None | None | N |
| M/E | 0.7673 | likely_pathogenic | 0.797 | pathogenic | -2.298 | Highly Destabilizing | 0.59 | D | 0.661 | neutral | None | None | None | None | N |
| M/F | 0.3936 | ambiguous | 0.3889 | ambiguous | -0.905 | Destabilizing | 0.009 | N | 0.318 | neutral | None | None | None | None | N |
| M/G | 0.8468 | likely_pathogenic | 0.8652 | pathogenic | -2.763 | Highly Destabilizing | 0.742 | D | 0.688 | prob.neutral | None | None | None | None | N |
| M/H | 0.6454 | likely_pathogenic | 0.6626 | pathogenic | -2.245 | Highly Destabilizing | 0.953 | D | 0.623 | neutral | None | None | None | None | N |
| M/I | 0.6132 | likely_pathogenic | 0.6699 | pathogenic | -1.292 | Destabilizing | 0.684 | D | 0.581 | neutral | N | 0.393861654 | None | None | N |
| M/K | 0.3093 | likely_benign | 0.3598 | ambiguous | -1.714 | Destabilizing | 0.003 | N | 0.415 | neutral | N | 0.395341734 | None | None | N |
| M/L | 0.2513 | likely_benign | 0.2868 | benign | -1.292 | Destabilizing | 0.164 | N | 0.397 | neutral | N | 0.454563396 | None | None | N |
| M/N | 0.8154 | likely_pathogenic | 0.8258 | pathogenic | -1.903 | Destabilizing | 0.91 | D | 0.663 | neutral | None | None | None | None | N |
| M/P | 0.9967 | likely_pathogenic | 0.9973 | pathogenic | -1.638 | Destabilizing | 0.953 | D | 0.673 | neutral | None | None | None | None | N |
| M/Q | 0.3339 | likely_benign | 0.3751 | ambiguous | -1.746 | Destabilizing | 0.742 | D | 0.671 | neutral | None | None | None | None | N |
| M/R | 0.3271 | likely_benign | 0.3583 | ambiguous | -1.57 | Destabilizing | 0.521 | D | 0.685 | prob.neutral | N | 0.381161716 | None | None | N |
| M/S | 0.5149 | ambiguous | 0.5526 | ambiguous | -2.413 | Highly Destabilizing | 0.742 | D | 0.667 | neutral | None | None | None | None | N |
| M/T | 0.3475 | ambiguous | 0.3967 | ambiguous | -2.154 | Highly Destabilizing | 0.684 | D | 0.688 | prob.neutral | N | 0.413908852 | None | None | N |
| M/V | 0.1871 | likely_benign | 0.213 | benign | -1.638 | Destabilizing | 0.472 | N | 0.552 | neutral | N | 0.397381962 | None | None | N |
| M/W | 0.7349 | likely_pathogenic | 0.7359 | pathogenic | -1.187 | Destabilizing | 0.996 | D | 0.657 | neutral | None | None | None | None | N |
| M/Y | 0.7015 | likely_pathogenic | 0.6995 | pathogenic | -1.204 | Destabilizing | 0.59 | D | 0.713 | prob.delet. | 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.