Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14478 | 43657;43658;43659 | chr2:178632574;178632573;178632572 | chr2:179497301;179497300;179497299 |
| N2AB | 12837 | 38734;38735;38736 | chr2:178632574;178632573;178632572 | chr2:179497301;179497300;179497299 |
| N2A | 11910 | 35953;35954;35955 | chr2:178632574;178632573;178632572 | chr2:179497301;179497300;179497299 |
| N2B | 5413 | 16462;16463;16464 | chr2:178632574;178632573;178632572 | chr2:179497301;179497300;179497299 |
| Novex-1 | 5538 | 16837;16838;16839 | chr2:178632574;178632573;178632572 | chr2:179497301;179497300;179497299 |
| Novex-2 | 5605 | 17038;17039;17040 | chr2:178632574;178632573;178632572 | chr2:179497301;179497300;179497299 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1307051231  |
-0.331 | None | D | 0.222 | 0.214 | 0.117506650769 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93424E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs1307051231 |
-0.331 | None | D | 0.222 | 0.214 | 0.117506650769 | gnomAD-4.0.0 | 6.57618E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.93424E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/K | rs1576690561 |
None | 0.055 | N | 0.539 | 0.359 | 0.714877521733 | gnomAD-4.0.0 | 1.59218E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43336E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3671 | ambiguous | 0.3609 | ambiguous | -2.288 | Highly Destabilizing | 0.007 | N | 0.393 | neutral | None | None | None | None | N |
| M/C | 0.7106 | likely_pathogenic | 0.6839 | pathogenic | -2.301 | Highly Destabilizing | 0.628 | D | 0.494 | neutral | None | None | None | None | N |
| M/D | 0.8093 | likely_pathogenic | 0.8011 | pathogenic | -1.885 | Destabilizing | 0.072 | N | 0.526 | neutral | None | None | None | None | N |
| M/E | 0.4854 | ambiguous | 0.4752 | ambiguous | -1.706 | Destabilizing | 0.072 | N | 0.549 | neutral | None | None | None | None | N |
| M/F | 0.2937 | likely_benign | 0.3043 | benign | -0.816 | Destabilizing | 0.072 | N | 0.495 | neutral | None | None | None | None | N |
| M/G | 0.6769 | likely_pathogenic | 0.6473 | pathogenic | -2.731 | Highly Destabilizing | 0.072 | N | 0.537 | neutral | None | None | None | None | N |
| M/H | 0.471 | ambiguous | 0.4589 | ambiguous | -2.152 | Highly Destabilizing | 0.628 | D | 0.517 | neutral | None | None | None | None | N |
| M/I | 0.1261 | likely_benign | 0.1251 | benign | -1.039 | Destabilizing | None | N | 0.222 | neutral | D | 0.528142257 | None | None | N |
| M/K | 0.2169 | likely_benign | 0.2105 | benign | -1.372 | Destabilizing | 0.055 | N | 0.539 | neutral | N | 0.50363618 | None | None | N |
| M/L | 0.1301 | likely_benign | 0.1273 | benign | -1.039 | Destabilizing | 0.001 | N | 0.281 | neutral | D | 0.546765284 | None | None | N |
| M/N | 0.4357 | ambiguous | 0.4323 | ambiguous | -1.572 | Destabilizing | 0.072 | N | 0.521 | neutral | None | None | None | None | N |
| M/P | 0.9715 | likely_pathogenic | 0.9694 | pathogenic | -1.435 | Destabilizing | 0.136 | N | 0.541 | neutral | None | None | None | None | N |
| M/Q | 0.2673 | likely_benign | 0.2599 | benign | -1.387 | Destabilizing | 0.136 | N | 0.515 | neutral | None | None | None | None | N |
| M/R | 0.2003 | likely_benign | 0.1947 | benign | -1.295 | Destabilizing | 0.106 | N | 0.507 | neutral | N | 0.517850565 | None | None | N |
| M/S | 0.3161 | likely_benign | 0.3202 | benign | -2.207 | Highly Destabilizing | 0.016 | N | 0.457 | neutral | None | None | None | None | N |
| M/T | 0.1484 | likely_benign | 0.1419 | benign | -1.906 | Destabilizing | None | N | 0.319 | neutral | N | 0.39574884 | None | None | N |
| M/V | 0.0774 | likely_benign | 0.0728 | benign | -1.435 | Destabilizing | 0.001 | N | 0.381 | neutral | N | 0.497400025 | None | None | N |
| M/W | 0.6231 | likely_pathogenic | 0.61 | pathogenic | -1.039 | Destabilizing | 0.864 | D | 0.489 | neutral | None | None | None | None | N |
| M/Y | 0.5413 | ambiguous | 0.5485 | ambiguous | -1.042 | Destabilizing | 0.356 | N | 0.534 | 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.