Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28697 | 86314;86315;86316 | chr2:178560043;178560042;178560041 | chr2:179424770;179424769;179424768 |
| N2AB | 27056 | 81391;81392;81393 | chr2:178560043;178560042;178560041 | chr2:179424770;179424769;179424768 |
| N2A | 26129 | 78610;78611;78612 | chr2:178560043;178560042;178560041 | chr2:179424770;179424769;179424768 |
| N2B | 19632 | 59119;59120;59121 | chr2:178560043;178560042;178560041 | chr2:179424770;179424769;179424768 |
| Novex-1 | 19757 | 59494;59495;59496 | chr2:178560043;178560042;178560041 | chr2:179424770;179424769;179424768 |
| Novex-2 | 19824 | 59695;59696;59697 | chr2:178560043;178560042;178560041 | chr2:179424770;179424769;179424768 |
| 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 | rs1559283455  |
None | 0.124 | N | 0.409 | 0.199 | 0.288727942641 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| D/A | rs1559283455 |
None | 0.124 | N | 0.409 | 0.199 | 0.288727942641 | 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 |
| D/A | rs1559283455 |
None | 0.124 | N | 0.409 | 0.199 | 0.288727942641 | gnomAD-4.0.0 | 6.57255E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46994E-05 | 0 | 0 |
| D/V | None | None | 0.497 | N | 0.545 | 0.291 | 0.449956787536 | gnomAD-4.0.0 | 6.84251E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52398E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | None | None | 0.859 | D | 0.588 | 0.332 | 0.568001609556 | gnomAD-4.0.0 | 1.59153E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4332E-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 | 0.1093 | likely_benign | 0.1074 | benign | -0.19 | Destabilizing | 0.124 | N | 0.409 | neutral | N | 0.471266432 | None | None | N |
| D/C | 0.3977 | ambiguous | 0.3795 | ambiguous | -0.186 | Destabilizing | 0.968 | D | 0.643 | neutral | None | None | None | None | N |
| D/E | 0.0833 | likely_benign | 0.0832 | benign | -0.115 | Destabilizing | None | N | 0.182 | neutral | N | 0.403731931 | None | None | N |
| D/F | 0.3979 | ambiguous | 0.3943 | ambiguous | -0.116 | Destabilizing | 0.89 | D | 0.581 | neutral | None | None | None | None | N |
| D/G | 0.1337 | likely_benign | 0.1327 | benign | -0.358 | Destabilizing | 0.124 | N | 0.357 | neutral | N | 0.467532693 | None | None | N |
| D/H | 0.1959 | likely_benign | 0.194 | benign | 0.308 | Stabilizing | 0.667 | D | 0.419 | neutral | N | 0.488294755 | None | None | N |
| D/I | 0.1688 | likely_benign | 0.1644 | benign | 0.201 | Stabilizing | 0.726 | D | 0.582 | neutral | None | None | None | None | N |
| D/K | 0.2118 | likely_benign | 0.2234 | benign | 0.172 | Stabilizing | 0.157 | N | 0.353 | neutral | None | None | None | None | N |
| D/L | 0.2032 | likely_benign | 0.2031 | benign | 0.201 | Stabilizing | 0.567 | D | 0.551 | neutral | None | None | None | None | N |
| D/M | 0.3567 | ambiguous | 0.354 | ambiguous | 0.095 | Stabilizing | 0.968 | D | 0.595 | neutral | None | None | None | None | N |
| D/N | 0.0906 | likely_benign | 0.0843 | benign | 0.023 | Stabilizing | 0.001 | N | 0.3 | neutral | N | 0.46237759 | None | None | N |
| D/P | 0.5102 | ambiguous | 0.5539 | ambiguous | 0.091 | Stabilizing | 0.726 | D | 0.415 | neutral | None | None | None | None | N |
| D/Q | 0.1866 | likely_benign | 0.1833 | benign | 0.049 | Stabilizing | 0.157 | N | 0.391 | neutral | None | None | None | None | N |
| D/R | 0.2604 | likely_benign | 0.2694 | benign | 0.471 | Stabilizing | 0.396 | N | 0.469 | neutral | None | None | None | None | N |
| D/S | 0.098 | likely_benign | 0.0938 | benign | -0.157 | Destabilizing | 0.157 | N | 0.394 | neutral | None | None | None | None | N |
| D/T | 0.1345 | likely_benign | 0.1272 | benign | -0.025 | Destabilizing | 0.272 | N | 0.373 | neutral | None | None | None | None | N |
| D/V | 0.1069 | likely_benign | 0.1058 | benign | 0.091 | Stabilizing | 0.497 | N | 0.545 | neutral | N | 0.483715654 | None | None | N |
| D/W | 0.7664 | likely_pathogenic | 0.7594 | pathogenic | -0.008 | Destabilizing | 0.968 | D | 0.645 | neutral | None | None | None | None | N |
| D/Y | 0.1767 | likely_benign | 0.1711 | benign | 0.115 | Stabilizing | 0.859 | D | 0.588 | neutral | D | 0.52383148 | 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.