Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14291 | 43096;43097;43098 | chr2:178633488;178633487;178633486 | chr2:179498215;179498214;179498213 |
| N2AB | 12650 | 38173;38174;38175 | chr2:178633488;178633487;178633486 | chr2:179498215;179498214;179498213 |
| N2A | 11723 | 35392;35393;35394 | chr2:178633488;178633487;178633486 | chr2:179498215;179498214;179498213 |
| N2B | 5226 | 15901;15902;15903 | chr2:178633488;178633487;178633486 | chr2:179498215;179498214;179498213 |
| Novex-1 | 5351 | 16276;16277;16278 | chr2:178633488;178633487;178633486 | chr2:179498215;179498214;179498213 |
| Novex-2 | 5418 | 16477;16478;16479 | chr2:178633488;178633487;178633486 | chr2:179498215;179498214;179498213 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/V | rs746486506  |
-0.677 | 0.004 | N | 0.183 | 0.141 | 0.288727942641 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/V | rs746486506 |
-0.677 | 0.004 | N | 0.183 | 0.141 | 0.288727942641 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs746486506 |
-0.677 | 0.004 | N | 0.183 | 0.141 | 0.288727942641 | gnomAD-4.0.0 | 5.57948E-06 | None | None | None | None | N | None | 1.33626E-05 | 3.33667E-05 | None | 0 | 0 | None | 0 | 0 | 2.54328E-06 | 3.29439E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4999 | ambiguous | 0.5392 | ambiguous | -1.655 | Destabilizing | 0.944 | D | 0.569 | neutral | None | None | None | None | N |
| A/D | 0.9237 | likely_pathogenic | 0.8732 | pathogenic | -3.038 | Highly Destabilizing | 0.69 | D | 0.619 | neutral | None | None | None | None | N |
| A/E | 0.8982 | likely_pathogenic | 0.8344 | pathogenic | -2.978 | Highly Destabilizing | 0.81 | D | 0.605 | neutral | D | 0.731609291 | None | None | N |
| A/F | 0.8366 | likely_pathogenic | 0.7624 | pathogenic | -1.085 | Destabilizing | 0.69 | D | 0.627 | neutral | None | None | None | None | N |
| A/G | 0.2101 | likely_benign | 0.182 | benign | -1.528 | Destabilizing | 0.549 | D | 0.532 | neutral | D | 0.731530003 | None | None | N |
| A/H | 0.9528 | likely_pathogenic | 0.9301 | pathogenic | -1.633 | Destabilizing | 0.981 | D | 0.56 | neutral | None | None | None | None | N |
| A/I | 0.3964 | ambiguous | 0.3299 | benign | -0.435 | Destabilizing | 0.008 | N | 0.414 | neutral | None | None | None | None | N |
| A/K | 0.9651 | likely_pathogenic | 0.9371 | pathogenic | -1.582 | Destabilizing | 0.69 | D | 0.612 | neutral | None | None | None | None | N |
| A/L | 0.4139 | ambiguous | 0.3553 | ambiguous | -0.435 | Destabilizing | 0.116 | N | 0.463 | neutral | None | None | None | None | N |
| A/M | 0.5059 | ambiguous | 0.4296 | ambiguous | -0.552 | Destabilizing | 0.818 | D | 0.61 | neutral | None | None | None | None | N |
| A/N | 0.7766 | likely_pathogenic | 0.6929 | pathogenic | -1.762 | Destabilizing | 0.69 | D | 0.628 | neutral | None | None | None | None | N |
| A/P | 0.6591 | likely_pathogenic | 0.4789 | ambiguous | -0.656 | Destabilizing | 0.773 | D | 0.629 | neutral | D | 0.590972032 | None | None | N |
| A/Q | 0.8978 | likely_pathogenic | 0.8621 | pathogenic | -1.846 | Destabilizing | 0.818 | D | 0.639 | neutral | None | None | None | None | N |
| A/R | 0.9417 | likely_pathogenic | 0.9049 | pathogenic | -1.285 | Destabilizing | 0.69 | D | 0.637 | neutral | None | None | None | None | N |
| A/S | 0.1852 | likely_benign | 0.1542 | benign | -1.99 | Destabilizing | 0.193 | N | 0.486 | neutral | D | 0.567985315 | None | None | N |
| A/T | 0.1285 | likely_benign | 0.1013 | benign | -1.848 | Destabilizing | 0.001 | N | 0.378 | neutral | N | 0.499418133 | None | None | N |
| A/V | 0.166 | likely_benign | 0.1407 | benign | -0.656 | Destabilizing | 0.004 | N | 0.183 | neutral | N | 0.442966479 | None | None | N |
| A/W | 0.9734 | likely_pathogenic | 0.959 | pathogenic | -1.631 | Destabilizing | 0.981 | D | 0.615 | neutral | None | None | None | None | N |
| A/Y | 0.9221 | likely_pathogenic | 0.8824 | pathogenic | -1.217 | Destabilizing | 0.818 | D | 0.627 | 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.