Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22877 | 68854;68855;68856 | chr2:178577797;178577796;178577795 | chr2:179442524;179442523;179442522 |
| N2AB | 21236 | 63931;63932;63933 | chr2:178577797;178577796;178577795 | chr2:179442524;179442523;179442522 |
| N2A | 20309 | 61150;61151;61152 | chr2:178577797;178577796;178577795 | chr2:179442524;179442523;179442522 |
| N2B | 13812 | 41659;41660;41661 | chr2:178577797;178577796;178577795 | chr2:179442524;179442523;179442522 |
| Novex-1 | 13937 | 42034;42035;42036 | chr2:178577797;178577796;178577795 | chr2:179442524;179442523;179442522 |
| Novex-2 | 14004 | 42235;42236;42237 | chr2:178577797;178577796;178577795 | chr2:179442524;179442523;179442522 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs776873491  |
-1.553 | 0.078 | N | 0.307 | 0.167 | 0.46512379133 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| I/M | rs776873491 |
-1.553 | 0.078 | N | 0.307 | 0.167 | 0.46512379133 | gnomAD-4.0.0 | 1.59314E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86077E-06 | 0 | 0 |
| I/V | rs879104670 |
-1.875 | 0.012 | N | 0.213 | 0.046 | None | gnomAD-3.1.2 | 1.99E-05 | None | None | None | None | N | None | 2.44E-05 | 6.58E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.48E-05 | 0 | 0 |
| I/V | rs879104670 |
-1.875 | 0.012 | N | 0.213 | 0.046 | None | gnomAD-4.0.0 | 6.20401E-06 | None | None | None | None | N | None | 1.34445E-05 | 1.67056E-05 | None | 0 | 0 | None | 0 | 0 | 6.78443E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3941 | ambiguous | 0.4876 | ambiguous | -2.478 | Highly Destabilizing | 0.543 | D | 0.643 | neutral | None | None | None | None | N |
| I/C | 0.7383 | likely_pathogenic | 0.7845 | pathogenic | -1.664 | Destabilizing | 0.996 | D | 0.671 | neutral | None | None | None | None | N |
| I/D | 0.8434 | likely_pathogenic | 0.9055 | pathogenic | -2.645 | Highly Destabilizing | 0.984 | D | 0.69 | prob.neutral | None | None | None | None | N |
| I/E | 0.75 | likely_pathogenic | 0.8307 | pathogenic | -2.496 | Highly Destabilizing | 0.953 | D | 0.702 | prob.neutral | None | None | None | None | N |
| I/F | 0.1612 | likely_benign | 0.1799 | benign | -1.559 | Destabilizing | 0.742 | D | 0.675 | neutral | None | None | None | None | N |
| I/G | 0.8269 | likely_pathogenic | 0.8818 | pathogenic | -2.947 | Highly Destabilizing | 0.953 | D | 0.697 | prob.neutral | None | None | None | None | N |
| I/H | 0.5834 | likely_pathogenic | 0.6553 | pathogenic | -2.277 | Highly Destabilizing | 0.996 | D | 0.673 | neutral | None | None | None | None | N |
| I/K | 0.7321 | likely_pathogenic | 0.8066 | pathogenic | -2.091 | Highly Destabilizing | 0.939 | D | 0.696 | prob.neutral | N | 0.483379745 | None | None | N |
| I/L | 0.1208 | likely_benign | 0.1479 | benign | -1.162 | Destabilizing | 0.001 | N | 0.237 | neutral | N | 0.505453576 | None | None | N |
| I/M | 0.0894 | likely_benign | 0.0943 | benign | -0.922 | Destabilizing | 0.078 | N | 0.307 | neutral | N | 0.480091744 | None | None | N |
| I/N | 0.4218 | ambiguous | 0.498 | ambiguous | -2.235 | Highly Destabilizing | 0.984 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/P | 0.9861 | likely_pathogenic | 0.9898 | pathogenic | -1.578 | Destabilizing | 0.984 | D | 0.687 | prob.neutral | None | None | None | None | N |
| I/Q | 0.6161 | likely_pathogenic | 0.6953 | pathogenic | -2.231 | Highly Destabilizing | 0.953 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/R | 0.6072 | likely_pathogenic | 0.6935 | pathogenic | -1.553 | Destabilizing | 0.939 | D | 0.69 | prob.neutral | N | 0.473149076 | None | None | N |
| I/S | 0.3476 | ambiguous | 0.4209 | ambiguous | -2.881 | Highly Destabilizing | 0.854 | D | 0.656 | neutral | None | None | None | None | N |
| I/T | 0.1694 | likely_benign | 0.2042 | benign | -2.608 | Highly Destabilizing | 0.684 | D | 0.687 | prob.neutral | N | 0.497834171 | None | None | N |
| I/V | 0.0779 | likely_benign | 0.0821 | benign | -1.578 | Destabilizing | 0.012 | N | 0.213 | neutral | N | 0.457585059 | None | None | N |
| I/W | 0.7456 | likely_pathogenic | 0.7825 | pathogenic | -1.89 | Destabilizing | 0.996 | D | 0.683 | prob.neutral | None | None | None | None | N |
| I/Y | 0.5059 | ambiguous | 0.5681 | pathogenic | -1.636 | Destabilizing | 0.953 | D | 0.71 | 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.