Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29477 | 88654;88655;88656 | chr2:178555030;178555029;178555028 | chr2:179419757;179419756;179419755 |
| N2AB | 27836 | 83731;83732;83733 | chr2:178555030;178555029;178555028 | chr2:179419757;179419756;179419755 |
| N2A | 26909 | 80950;80951;80952 | chr2:178555030;178555029;178555028 | chr2:179419757;179419756;179419755 |
| N2B | 20412 | 61459;61460;61461 | chr2:178555030;178555029;178555028 | chr2:179419757;179419756;179419755 |
| Novex-1 | 20537 | 61834;61835;61836 | chr2:178555030;178555029;178555028 | chr2:179419757;179419756;179419755 |
| Novex-2 | 20604 | 62035;62036;62037 | chr2:178555030;178555029;178555028 | chr2:179419757;179419756;179419755 |
| 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/E | None | None | 0.977 | N | 0.381 | 0.206 | 0.202949470691 | gnomAD-4.0.0 | 3.18292E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71608E-06 | 0 | 0 |
| D/G | None | None | 0.955 | N | 0.523 | 0.343 | 0.19670166235 | gnomAD-4.0.0 | 6.84242E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65684E-05 |
| D/H | None | None | 0.999 | N | 0.6 | 0.344 | 0.26547132957 | gnomAD-4.0.0 | 1.36849E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99449E-07 | 1.15939E-05 | 0 |
| D/V | rs777351270  |
0.103 | 0.997 | N | 0.683 | 0.474 | 0.554315986709 | 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 |
| D/V | rs777351270 |
0.103 | 0.997 | N | 0.683 | 0.474 | 0.554315986709 | gnomAD-4.0.0 | 6.84242E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15939E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2797 | likely_benign | 0.2308 | benign | -0.524 | Destabilizing | 0.993 | D | 0.589 | neutral | N | 0.491230698 | None | None | N |
| D/C | 0.6652 | likely_pathogenic | 0.6076 | pathogenic | -0.131 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| D/E | 0.2654 | likely_benign | 0.244 | benign | -0.417 | Destabilizing | 0.977 | D | 0.381 | neutral | N | 0.492172061 | None | None | N |
| D/F | 0.8027 | likely_pathogenic | 0.7506 | pathogenic | -0.267 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| D/G | 0.1275 | likely_benign | 0.1031 | benign | -0.786 | Destabilizing | 0.955 | D | 0.523 | neutral | N | 0.470044563 | None | None | N |
| D/H | 0.5165 | ambiguous | 0.4443 | ambiguous | -0.325 | Destabilizing | 0.999 | D | 0.6 | neutral | N | 0.484590605 | None | None | N |
| D/I | 0.7566 | likely_pathogenic | 0.6949 | pathogenic | 0.141 | Stabilizing | 0.998 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/K | 0.6009 | likely_pathogenic | 0.526 | ambiguous | -0.076 | Destabilizing | 0.995 | D | 0.581 | neutral | None | None | None | None | N |
| D/L | 0.6335 | likely_pathogenic | 0.5618 | ambiguous | 0.141 | Stabilizing | 0.998 | D | 0.683 | prob.neutral | None | None | None | None | N |
| D/M | 0.7931 | likely_pathogenic | 0.7391 | pathogenic | 0.42 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| D/N | 0.1108 | likely_benign | 0.0925 | benign | -0.422 | Destabilizing | 0.117 | N | 0.292 | neutral | N | 0.466193394 | None | None | N |
| D/P | 0.9698 | likely_pathogenic | 0.9595 | pathogenic | -0.057 | Destabilizing | 0.999 | D | 0.612 | neutral | None | None | None | None | N |
| D/Q | 0.516 | ambiguous | 0.4462 | ambiguous | -0.339 | Destabilizing | 0.998 | D | 0.549 | neutral | None | None | None | None | N |
| D/R | 0.6009 | likely_pathogenic | 0.5242 | ambiguous | 0.126 | Stabilizing | 0.995 | D | 0.632 | neutral | None | None | None | None | N |
| D/S | 0.2172 | likely_benign | 0.1821 | benign | -0.579 | Destabilizing | 0.966 | D | 0.475 | neutral | None | None | None | None | N |
| D/T | 0.5706 | likely_pathogenic | 0.5157 | ambiguous | -0.37 | Destabilizing | 0.995 | D | 0.573 | neutral | None | None | None | None | N |
| D/V | 0.5448 | ambiguous | 0.4785 | ambiguous | -0.057 | Destabilizing | 0.997 | D | 0.683 | prob.neutral | N | 0.462131484 | None | None | N |
| D/W | 0.9317 | likely_pathogenic | 0.9105 | pathogenic | -0.074 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| D/Y | 0.3587 | ambiguous | 0.3141 | benign | -0.032 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.484844095 | 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.