Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6490 | 19693;19694;19695 | chr2:178728356;178728355;178728354 | chr2:179593083;179593082;179593081 |
| N2AB | 6173 | 18742;18743;18744 | chr2:178728356;178728355;178728354 | chr2:179593083;179593082;179593081 |
| N2A | 5246 | 15961;15962;15963 | chr2:178728356;178728355;178728354 | chr2:179593083;179593082;179593081 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | rs746981434  |
-0.872 | 0.023 | N | 0.165 | 0.236 | 0.359963025489 | gnomAD-2.1.1 | 4.21E-06 | None | None | None | None | N | None | 0 | 0 | None | 1.05664E-04 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs746981434 |
-0.872 | 0.023 | N | 0.165 | 0.236 | 0.359963025489 | gnomAD-4.0.0 | 4.83993E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.71628E-05 | 0 | None | 0 | 0 | 2.88414E-06 | 0 | 0 |
| M/T | rs769527897 |
-0.773 | 0.023 | N | 0.225 | 0.353 | 0.689162798981 | gnomAD-2.1.1 | 8.48E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.87E-05 | 0 |
| M/T | rs769527897 |
-0.773 | 0.023 | N | 0.225 | 0.353 | 0.689162798981 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/T | rs769527897 |
-0.773 | 0.023 | N | 0.225 | 0.353 | 0.689162798981 | gnomAD-4.0.0 | 4.364E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.95161E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3407 | ambiguous | 0.4125 | ambiguous | -2.352 | Highly Destabilizing | 0.495 | N | 0.389 | neutral | None | None | None | None | N |
| M/C | 0.8152 | likely_pathogenic | 0.8495 | pathogenic | -1.506 | Destabilizing | 0.995 | D | 0.431 | neutral | None | None | None | None | N |
| M/D | 0.7744 | likely_pathogenic | 0.8279 | pathogenic | -1.084 | Destabilizing | 0.704 | D | 0.491 | neutral | None | None | None | None | N |
| M/E | 0.3988 | ambiguous | 0.4602 | ambiguous | -1.032 | Destabilizing | 0.543 | D | 0.43 | neutral | None | None | None | None | N |
| M/F | 0.3033 | likely_benign | 0.3744 | ambiguous | -1.223 | Destabilizing | 0.944 | D | 0.479 | neutral | None | None | None | None | N |
| M/G | 0.639 | likely_pathogenic | 0.7182 | pathogenic | -2.696 | Highly Destabilizing | 0.704 | D | 0.47 | neutral | None | None | None | None | N |
| M/H | 0.511 | ambiguous | 0.5937 | pathogenic | -1.688 | Destabilizing | 0.981 | D | 0.439 | neutral | None | None | None | None | N |
| M/I | 0.2147 | likely_benign | 0.2707 | benign | -1.43 | Destabilizing | 0.023 | N | 0.165 | neutral | N | 0.4632341 | None | None | N |
| M/K | 0.1655 | likely_benign | 0.2002 | benign | -1.073 | Destabilizing | 0.006 | N | 0.233 | neutral | N | 0.506526304 | None | None | N |
| M/L | 0.1231 | likely_benign | 0.1293 | benign | -1.43 | Destabilizing | 0.139 | N | 0.281 | neutral | N | 0.474296455 | None | None | N |
| M/N | 0.4601 | ambiguous | 0.5577 | ambiguous | -0.93 | Destabilizing | 0.704 | D | 0.453 | neutral | None | None | None | None | N |
| M/P | 0.8957 | likely_pathogenic | 0.9123 | pathogenic | -1.714 | Destabilizing | 0.944 | D | 0.465 | neutral | None | None | None | None | N |
| M/Q | 0.2317 | likely_benign | 0.2695 | benign | -0.991 | Destabilizing | 0.704 | D | 0.467 | neutral | None | None | None | None | N |
| M/R | 0.1853 | likely_benign | 0.2344 | benign | -0.542 | Destabilizing | 0.473 | N | 0.453 | neutral | N | 0.493501078 | None | None | N |
| M/S | 0.3941 | ambiguous | 0.4939 | ambiguous | -1.561 | Destabilizing | 0.329 | N | 0.411 | neutral | None | None | None | None | N |
| M/T | 0.1673 | likely_benign | 0.203 | benign | -1.395 | Destabilizing | 0.023 | N | 0.225 | neutral | N | 0.417752526 | None | None | N |
| M/V | 0.0973 | likely_benign | 0.1105 | benign | -1.714 | Destabilizing | 0.139 | N | 0.317 | neutral | N | 0.426462436 | None | None | N |
| M/W | 0.5436 | ambiguous | 0.6221 | pathogenic | -1.124 | Destabilizing | 0.995 | D | 0.425 | neutral | None | None | None | None | N |
| M/Y | 0.5453 | ambiguous | 0.6136 | pathogenic | -1.239 | Destabilizing | 0.981 | D | 0.455 | 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.