Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4810 | 14653;14654;14655 | chr2:178736018;178736017;178736016 | chr2:179600745;179600744;179600743 |
| N2AB | 4493 | 13702;13703;13704 | chr2:178736018;178736017;178736016 | chr2:179600745;179600744;179600743 |
| N2A | 3566 | 10921;10922;10923 | chr2:178736018;178736017;178736016 | chr2:179600745;179600744;179600743 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/Q | rs367630668  |
-0.452 | 0.957 | N | 0.307 | 0.212 | 0.0401082797425 | gnomAD-2.1.1 | 6.82E-05 | None | None | None | None | I | None | 8.28E-05 | 3.69654E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 5.64972E-04 |
| K/Q | rs367630668 |
-0.452 | 0.957 | N | 0.307 | 0.212 | 0.0401082797425 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 7.24E-05 | 1.96515E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/Q | rs367630668 |
-0.452 | 0.957 | N | 0.307 | 0.212 | 0.0401082797425 | gnomAD-4.0.0 | 1.67492E-05 | None | None | None | None | I | None | 4.00716E-05 | 3.8414E-04 | None | 0 | 0 | None | 0 | 0 | 8.48355E-07 | 0 | 0 |
| K/R | rs375443901 |
-0.374 | 0.996 | N | 0.471 | 0.211 | 0.0297737177859 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/R | rs375443901 |
-0.374 | 0.996 | N | 0.471 | 0.211 | 0.0297737177859 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs375443901 |
-0.374 | 0.996 | N | 0.471 | 0.211 | 0.0297737177859 | gnomAD-4.0.0 | 7.70323E-06 | None | None | None | None | I | None | 1.01537E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.6272 | likely_pathogenic | 0.6874 | pathogenic | -0.195 | Destabilizing | 0.997 | D | 0.517 | neutral | None | None | None | None | I |
| K/C | 0.8799 | likely_pathogenic | 0.9048 | pathogenic | -0.414 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| K/D | 0.7414 | likely_pathogenic | 0.8019 | pathogenic | 0.259 | Stabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | I |
| K/E | 0.2695 | likely_benign | 0.3408 | ambiguous | 0.31 | Stabilizing | 0.992 | D | 0.448 | neutral | N | 0.390995118 | None | None | I |
| K/F | 0.9132 | likely_pathogenic | 0.9343 | pathogenic | -0.2 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| K/G | 0.6484 | likely_pathogenic | 0.7071 | pathogenic | -0.455 | Destabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | I |
| K/H | 0.4615 | ambiguous | 0.4701 | ambiguous | -0.648 | Destabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | I |
| K/I | 0.682 | likely_pathogenic | 0.7643 | pathogenic | 0.429 | Stabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| K/L | 0.6322 | likely_pathogenic | 0.6866 | pathogenic | 0.429 | Stabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | I |
| K/M | 0.4218 | ambiguous | 0.5025 | ambiguous | 0.136 | Stabilizing | 1.0 | D | 0.602 | neutral | N | 0.455827589 | None | None | I |
| K/N | 0.5569 | ambiguous | 0.639 | pathogenic | -0.012 | Destabilizing | 0.999 | D | 0.621 | neutral | N | 0.449964264 | None | None | I |
| K/P | 0.9532 | likely_pathogenic | 0.9676 | pathogenic | 0.251 | Stabilizing | 1.0 | D | 0.618 | neutral | None | None | None | None | I |
| K/Q | 0.2009 | likely_benign | 0.2251 | benign | -0.118 | Destabilizing | 0.957 | D | 0.307 | neutral | N | 0.428608321 | None | None | I |
| K/R | 0.1058 | likely_benign | 0.1049 | benign | -0.149 | Destabilizing | 0.996 | D | 0.471 | neutral | N | 0.452113851 | None | None | I |
| K/S | 0.6158 | likely_pathogenic | 0.6783 | pathogenic | -0.605 | Destabilizing | 0.997 | D | 0.531 | neutral | None | None | None | None | I |
| K/T | 0.3982 | ambiguous | 0.4723 | ambiguous | -0.376 | Destabilizing | 0.999 | D | 0.593 | neutral | N | 0.450160191 | None | None | I |
| K/V | 0.6312 | likely_pathogenic | 0.7101 | pathogenic | 0.251 | Stabilizing | 1.0 | D | 0.634 | neutral | None | None | None | None | I |
| K/W | 0.9108 | likely_pathogenic | 0.9322 | pathogenic | -0.154 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| K/Y | 0.8009 | likely_pathogenic | 0.8421 | pathogenic | 0.174 | Stabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | I |
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.