Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18696 | 56311;56312;56313 | chr2:178599815;178599814;178599813 | chr2:179464542;179464541;179464540 |
| N2AB | 17055 | 51388;51389;51390 | chr2:178599815;178599814;178599813 | chr2:179464542;179464541;179464540 |
| N2A | 16128 | 48607;48608;48609 | chr2:178599815;178599814;178599813 | chr2:179464542;179464541;179464540 |
| N2B | 9631 | 29116;29117;29118 | chr2:178599815;178599814;178599813 | chr2:179464542;179464541;179464540 |
| Novex-1 | 9756 | 29491;29492;29493 | chr2:178599815;178599814;178599813 | chr2:179464542;179464541;179464540 |
| Novex-2 | 9823 | 29692;29693;29694 | chr2:178599815;178599814;178599813 | chr2:179464542;179464541;179464540 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs1433208414  |
None | 0.989 | D | 0.627 | 0.621 | 0.888587291134 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/F | rs1433208414 |
None | 0.989 | D | 0.627 | 0.621 | 0.888587291134 | gnomAD-4.0.0 | 1.24889E-06 | None | None | None | None | N | None | 1.35102E-05 | 1.73118E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | None | None | 0.891 | N | 0.439 | 0.279 | 0.562428738172 | gnomAD-4.0.0 | 6.89932E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.03388E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1394 | likely_benign | 0.1467 | benign | -1.749 | Destabilizing | 0.267 | N | 0.363 | neutral | N | 0.493389222 | None | None | N |
| V/C | 0.7656 | likely_pathogenic | 0.7852 | pathogenic | -1.238 | Destabilizing | 0.998 | D | 0.559 | neutral | None | None | None | None | N |
| V/D | 0.5802 | likely_pathogenic | 0.704 | pathogenic | -1.843 | Destabilizing | 0.669 | D | 0.567 | neutral | D | 0.536586778 | None | None | N |
| V/E | 0.4195 | ambiguous | 0.5503 | ambiguous | -1.821 | Destabilizing | 0.016 | N | 0.371 | neutral | None | None | None | None | N |
| V/F | 0.3713 | ambiguous | 0.4063 | ambiguous | -1.33 | Destabilizing | 0.989 | D | 0.627 | neutral | D | 0.524470004 | None | None | N |
| V/G | 0.2792 | likely_benign | 0.305 | benign | -2.097 | Highly Destabilizing | 0.002 | N | 0.34 | neutral | N | 0.50601459 | None | None | N |
| V/H | 0.8038 | likely_pathogenic | 0.8718 | pathogenic | -1.624 | Destabilizing | 0.974 | D | 0.601 | neutral | None | None | None | None | N |
| V/I | 0.1095 | likely_benign | 0.1042 | benign | -0.875 | Destabilizing | 0.891 | D | 0.439 | neutral | N | 0.498488398 | None | None | N |
| V/K | 0.5095 | ambiguous | 0.6702 | pathogenic | -1.487 | Destabilizing | 0.728 | D | 0.559 | neutral | None | None | None | None | N |
| V/L | 0.4141 | ambiguous | 0.4502 | ambiguous | -0.875 | Destabilizing | 0.625 | D | 0.441 | neutral | N | 0.511110978 | None | None | N |
| V/M | 0.2284 | likely_benign | 0.2448 | benign | -0.677 | Destabilizing | 0.991 | D | 0.535 | neutral | None | None | None | None | N |
| V/N | 0.5325 | ambiguous | 0.6498 | pathogenic | -1.332 | Destabilizing | 0.842 | D | 0.633 | neutral | None | None | None | None | N |
| V/P | 0.9408 | likely_pathogenic | 0.9694 | pathogenic | -1.133 | Destabilizing | 0.974 | D | 0.629 | neutral | None | None | None | None | N |
| V/Q | 0.5118 | ambiguous | 0.6337 | pathogenic | -1.5 | Destabilizing | 0.904 | D | 0.628 | neutral | None | None | None | None | N |
| V/R | 0.513 | ambiguous | 0.6609 | pathogenic | -0.938 | Destabilizing | 0.949 | D | 0.647 | neutral | None | None | None | None | N |
| V/S | 0.3093 | likely_benign | 0.3665 | ambiguous | -1.861 | Destabilizing | 0.172 | N | 0.375 | neutral | None | None | None | None | N |
| V/T | 0.1448 | likely_benign | 0.1706 | benign | -1.733 | Destabilizing | 0.728 | D | 0.425 | neutral | None | None | None | None | N |
| V/W | 0.9339 | likely_pathogenic | 0.9523 | pathogenic | -1.557 | Destabilizing | 0.998 | D | 0.581 | neutral | None | None | None | None | N |
| V/Y | 0.7621 | likely_pathogenic | 0.8215 | pathogenic | -1.276 | Destabilizing | 0.991 | D | 0.63 | 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.