Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33278 | 100057;100058;100059 | chr2:178537375;178537374;178537373 | chr2:179402102;179402101;179402100 |
| N2AB | 31637 | 95134;95135;95136 | chr2:178537375;178537374;178537373 | chr2:179402102;179402101;179402100 |
| N2A | 30710 | 92353;92354;92355 | chr2:178537375;178537374;178537373 | chr2:179402102;179402101;179402100 |
| N2B | 24213 | 72862;72863;72864 | chr2:178537375;178537374;178537373 | chr2:179402102;179402101;179402100 |
| Novex-1 | 24338 | 73237;73238;73239 | chr2:178537375;178537374;178537373 | chr2:179402102;179402101;179402100 |
| Novex-2 | 24405 | 73438;73439;73440 | chr2:178537375;178537374;178537373 | chr2:179402102;179402101;179402100 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs749065018  |
-0.513 | 0.336 | N | 0.52 | 0.144 | 0.299427821978 | gnomAD-2.1.1 | 4.19E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.69E-05 | None | 0 | None | 0 | 0 | 0 |
| T/R | rs772862798 |
0.018 | 0.997 | N | 0.653 | 0.482 | 0.789031109301 | gnomAD-2.1.1 | 8.41E-06 | None | None | None | None | I | None | 0 | 6.09E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/R | rs772862798 |
0.018 | 0.997 | N | 0.653 | 0.482 | 0.789031109301 | gnomAD-4.0.0 | 3.28861E-06 | None | None | None | None | I | None | 0 | 4.76894E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0987 | likely_benign | 0.0989 | benign | -0.375 | Destabilizing | 0.336 | N | 0.52 | neutral | N | 0.493885081 | None | None | I |
| T/C | 0.4945 | ambiguous | 0.4932 | ambiguous | -0.161 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| T/D | 0.4598 | ambiguous | 0.4409 | ambiguous | 0.002 | Stabilizing | 0.972 | D | 0.605 | neutral | None | None | None | None | I |
| T/E | 0.3298 | likely_benign | 0.318 | benign | -0.089 | Destabilizing | 0.992 | D | 0.603 | neutral | None | None | None | None | I |
| T/F | 0.34 | likely_benign | 0.3438 | ambiguous | -0.959 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| T/G | 0.3633 | ambiguous | 0.3581 | ambiguous | -0.477 | Destabilizing | 0.977 | D | 0.608 | neutral | None | None | None | None | I |
| T/H | 0.2567 | likely_benign | 0.2407 | benign | -0.842 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| T/I | 0.21 | likely_benign | 0.2201 | benign | -0.225 | Destabilizing | 0.996 | D | 0.66 | neutral | D | 0.524901421 | None | None | I |
| T/K | 0.1564 | likely_benign | 0.1534 | benign | -0.32 | Destabilizing | 0.992 | D | 0.607 | neutral | N | 0.458614927 | None | None | I |
| T/L | 0.1578 | likely_benign | 0.1618 | benign | -0.225 | Destabilizing | 0.979 | D | 0.594 | neutral | None | None | None | None | I |
| T/M | 0.0985 | likely_benign | 0.1042 | benign | 0.087 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| T/N | 0.1354 | likely_benign | 0.128 | benign | -0.052 | Destabilizing | 0.972 | D | 0.655 | neutral | None | None | None | None | I |
| T/P | 0.3489 | ambiguous | 0.4477 | ambiguous | -0.248 | Destabilizing | 0.982 | D | 0.649 | neutral | N | 0.487378304 | None | None | I |
| T/Q | 0.2022 | likely_benign | 0.1974 | benign | -0.338 | Destabilizing | 0.994 | D | 0.673 | neutral | None | None | None | None | I |
| T/R | 0.1261 | likely_benign | 0.1332 | benign | -0.032 | Destabilizing | 0.997 | D | 0.653 | neutral | N | 0.471605654 | None | None | I |
| T/S | 0.1301 | likely_benign | 0.1226 | benign | -0.237 | Destabilizing | 0.032 | N | 0.382 | neutral | N | 0.468333275 | None | None | I |
| T/V | 0.1717 | likely_benign | 0.1708 | benign | -0.248 | Destabilizing | 0.971 | D | 0.599 | neutral | None | None | None | None | I |
| T/W | 0.7173 | likely_pathogenic | 0.7303 | pathogenic | -0.964 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| T/Y | 0.3769 | ambiguous | 0.3783 | ambiguous | -0.676 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | 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.