Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13746 | 41461;41462;41463 | chr2:178636491;178636490;178636489 | chr2:179501218;179501217;179501216 |
| N2AB | 12105 | 36538;36539;36540 | chr2:178636491;178636490;178636489 | chr2:179501218;179501217;179501216 |
| N2A | 11178 | 33757;33758;33759 | chr2:178636491;178636490;178636489 | chr2:179501218;179501217;179501216 |
| N2B | 4681 | 14266;14267;14268 | chr2:178636491;178636490;178636489 | chr2:179501218;179501217;179501216 |
| Novex-1 | 4806 | 14641;14642;14643 | chr2:178636491;178636490;178636489 | chr2:179501218;179501217;179501216 |
| Novex-2 | 4873 | 14842;14843;14844 | chr2:178636491;178636490;178636489 | chr2:179501218;179501217;179501216 |
| 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 | rs1177814929  |
-0.64 | 0.009 | N | 0.262 | 0.111 | 0.3691244813 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/M | rs1177814929 |
-0.64 | 0.009 | N | 0.262 | 0.111 | 0.3691244813 | gnomAD-4.0.0 | 1.59206E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43303E-05 | 0 |
| I/T | None | None | 0.22 | N | 0.562 | 0.325 | 0.704985832586 | gnomAD-4.0.0 | 2.7375E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7993E-06 | 1.15953E-05 | 1.65722E-05 |
| I/V | rs554128863 |
-1.18 | 0.025 | N | 0.243 | 0.099 | 0.496495002422 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs554128863 |
-1.18 | 0.025 | N | 0.243 | 0.099 | 0.496495002422 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| I/V | rs554128863 |
-1.18 | 0.025 | N | 0.243 | 0.099 | 0.496495002422 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| I/V | rs554128863 |
-1.18 | 0.025 | N | 0.243 | 0.099 | 0.496495002422 | gnomAD-4.0.0 | 6.56978E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 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 | 0.4101 | ambiguous | 0.5665 | pathogenic | -1.832 | Destabilizing | 0.001 | N | 0.243 | neutral | None | None | None | None | N |
| I/C | 0.866 | likely_pathogenic | 0.93 | pathogenic | -1.12 | Destabilizing | 0.909 | D | 0.612 | neutral | None | None | None | None | N |
| I/D | 0.8832 | likely_pathogenic | 0.9444 | pathogenic | -1.814 | Destabilizing | 0.726 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/E | 0.7483 | likely_pathogenic | 0.8605 | pathogenic | -1.823 | Destabilizing | 0.567 | D | 0.671 | neutral | None | None | None | None | N |
| I/F | 0.2556 | likely_benign | 0.3905 | ambiguous | -1.474 | Destabilizing | 0.497 | N | 0.541 | neutral | N | 0.505109155 | None | None | N |
| I/G | 0.7984 | likely_pathogenic | 0.8998 | pathogenic | -2.156 | Highly Destabilizing | 0.157 | N | 0.627 | neutral | None | None | None | None | N |
| I/H | 0.7278 | likely_pathogenic | 0.8644 | pathogenic | -1.42 | Destabilizing | 0.968 | D | 0.672 | neutral | None | None | None | None | N |
| I/K | 0.6339 | likely_pathogenic | 0.79 | pathogenic | -1.229 | Destabilizing | 0.567 | D | 0.643 | neutral | None | None | None | None | N |
| I/L | 0.143 | likely_benign | 0.1895 | benign | -1.003 | Destabilizing | 0.009 | N | 0.217 | neutral | N | 0.470419325 | None | None | N |
| I/M | 0.092 | likely_benign | 0.1358 | benign | -0.634 | Destabilizing | 0.009 | N | 0.262 | neutral | N | 0.491522583 | None | None | N |
| I/N | 0.507 | ambiguous | 0.6754 | pathogenic | -1.053 | Destabilizing | 0.667 | D | 0.695 | prob.neutral | N | 0.465400314 | None | None | N |
| I/P | 0.9158 | likely_pathogenic | 0.9524 | pathogenic | -1.251 | Destabilizing | 0.726 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/Q | 0.5831 | likely_pathogenic | 0.7564 | pathogenic | -1.3 | Destabilizing | 0.567 | D | 0.694 | prob.neutral | None | None | None | None | N |
| I/R | 0.5146 | ambiguous | 0.6974 | pathogenic | -0.579 | Destabilizing | 0.567 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/S | 0.3895 | ambiguous | 0.5554 | ambiguous | -1.618 | Destabilizing | 0.124 | N | 0.629 | neutral | N | 0.441133524 | None | None | N |
| I/T | 0.2302 | likely_benign | 0.3187 | benign | -1.518 | Destabilizing | 0.22 | N | 0.562 | neutral | N | 0.454405202 | None | None | N |
| I/V | 0.1273 | likely_benign | 0.1511 | benign | -1.251 | Destabilizing | 0.025 | N | 0.243 | neutral | N | 0.483578849 | None | None | N |
| I/W | 0.8283 | likely_pathogenic | 0.9206 | pathogenic | -1.579 | Destabilizing | 0.968 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/Y | 0.6774 | likely_pathogenic | 0.8307 | pathogenic | -1.352 | Destabilizing | 0.726 | D | 0.623 | 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.