Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25134 | 75625;75626;75627 | chr2:178570732;178570731;178570730 | chr2:179435459;179435458;179435457 |
| N2AB | 23493 | 70702;70703;70704 | chr2:178570732;178570731;178570730 | chr2:179435459;179435458;179435457 |
| N2A | 22566 | 67921;67922;67923 | chr2:178570732;178570731;178570730 | chr2:179435459;179435458;179435457 |
| N2B | 16069 | 48430;48431;48432 | chr2:178570732;178570731;178570730 | chr2:179435459;179435458;179435457 |
| Novex-1 | 16194 | 48805;48806;48807 | chr2:178570732;178570731;178570730 | chr2:179435459;179435458;179435457 |
| Novex-2 | 16261 | 49006;49007;49008 | chr2:178570732;178570731;178570730 | chr2:179435459;179435458;179435457 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | rs746343685  |
None | 0.016 | N | 0.333 | 0.193 | 0.343788945184 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/A | rs746343685 |
None | 0.016 | N | 0.333 | 0.193 | 0.343788945184 | gnomAD-4.0.0 | 6.5754E-06 | None | None | None | None | N | None | 0 | 6.55738E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs746343685 |
-0.736 | 0.002 | N | 0.251 | 0.212 | 0.208816687407 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/G | rs746343685 |
-0.736 | 0.002 | N | 0.251 | 0.212 | 0.208816687407 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/G | rs746343685 |
-0.736 | 0.002 | N | 0.251 | 0.212 | 0.208816687407 | gnomAD-4.0.0 | 2.56289E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78785E-06 | 0 | 0 |
| D/H | None | None | 0.896 | N | 0.561 | 0.283 | 0.298745278005 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.75482E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2216 | likely_benign | 0.2141 | benign | -0.557 | Destabilizing | 0.016 | N | 0.333 | neutral | N | 0.485630957 | None | None | N |
| D/C | 0.6754 | likely_pathogenic | 0.6898 | pathogenic | -0.189 | Destabilizing | 0.992 | D | 0.567 | neutral | None | None | None | None | N |
| D/E | 0.2916 | likely_benign | 0.2839 | benign | -0.535 | Destabilizing | 0.004 | N | 0.173 | neutral | N | 0.47883827 | None | None | N |
| D/F | 0.6457 | likely_pathogenic | 0.654 | pathogenic | -0.121 | Destabilizing | 0.972 | D | 0.577 | neutral | None | None | None | None | N |
| D/G | 0.2598 | likely_benign | 0.2508 | benign | -0.895 | Destabilizing | 0.002 | N | 0.251 | neutral | N | 0.50920125 | None | None | N |
| D/H | 0.3463 | ambiguous | 0.3498 | ambiguous | -0.361 | Destabilizing | 0.896 | D | 0.561 | neutral | N | 0.501851203 | None | None | N |
| D/I | 0.4429 | ambiguous | 0.4459 | ambiguous | 0.33 | Stabilizing | 0.92 | D | 0.588 | neutral | None | None | None | None | N |
| D/K | 0.4987 | ambiguous | 0.5065 | ambiguous | -0.212 | Destabilizing | 0.447 | N | 0.487 | neutral | None | None | None | None | N |
| D/L | 0.4712 | ambiguous | 0.4781 | ambiguous | 0.33 | Stabilizing | 0.617 | D | 0.569 | neutral | None | None | None | None | N |
| D/M | 0.6678 | likely_pathogenic | 0.6685 | pathogenic | 0.69 | Stabilizing | 0.992 | D | 0.567 | neutral | None | None | None | None | N |
| D/N | 0.1167 | likely_benign | 0.1182 | benign | -0.675 | Destabilizing | 0.549 | D | 0.376 | neutral | N | 0.497386746 | None | None | N |
| D/P | 0.9329 | likely_pathogenic | 0.9326 | pathogenic | 0.059 | Stabilizing | 0.92 | D | 0.559 | neutral | None | None | None | None | N |
| D/Q | 0.4699 | ambiguous | 0.4693 | ambiguous | -0.546 | Destabilizing | 0.739 | D | 0.473 | neutral | None | None | None | None | N |
| D/R | 0.5214 | ambiguous | 0.5227 | ambiguous | -0.025 | Destabilizing | 0.85 | D | 0.567 | neutral | None | None | None | None | N |
| D/S | 0.1688 | likely_benign | 0.1666 | benign | -0.903 | Destabilizing | 0.059 | N | 0.197 | neutral | None | None | None | None | N |
| D/T | 0.3262 | likely_benign | 0.3288 | benign | -0.625 | Destabilizing | 0.447 | N | 0.491 | neutral | None | None | None | None | N |
| D/V | 0.2734 | likely_benign | 0.2736 | benign | 0.059 | Stabilizing | 0.549 | D | 0.577 | neutral | N | 0.498426896 | None | None | N |
| D/W | 0.9148 | likely_pathogenic | 0.9195 | pathogenic | 0.101 | Stabilizing | 0.992 | D | 0.631 | neutral | None | None | None | None | N |
| D/Y | 0.2561 | likely_benign | 0.2611 | benign | 0.135 | Stabilizing | 0.963 | D | 0.573 | neutral | D | 0.524458704 | 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.