Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16149 | 48670;48671;48672 | chr2:178615656;178615655;178615654 | chr2:179480383;179480382;179480381 |
| N2AB | 14508 | 43747;43748;43749 | chr2:178615656;178615655;178615654 | chr2:179480383;179480382;179480381 |
| N2A | 13581 | 40966;40967;40968 | chr2:178615656;178615655;178615654 | chr2:179480383;179480382;179480381 |
| N2B | 7084 | 21475;21476;21477 | chr2:178615656;178615655;178615654 | chr2:179480383;179480382;179480381 |
| Novex-1 | 7209 | 21850;21851;21852 | chr2:178615656;178615655;178615654 | chr2:179480383;179480382;179480381 |
| Novex-2 | 7276 | 22051;22052;22053 | chr2:178615656;178615655;178615654 | chr2:179480383;179480382;179480381 |
| 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 | rs2057204111  |
None | 0.013 | N | 0.092 | 0.127 | 0.374434639691 | gnomAD-4.0.0 | 2.05432E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70027E-06 | 0 | 0 |
| M/R | rs760582847 |
-1.451 | 0.981 | N | 0.63 | 0.337 | 0.582449840715 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/R | rs760582847 |
-1.451 | 0.981 | N | 0.63 | 0.337 | 0.582449840715 | gnomAD-4.0.0 | 1.36952E-06 | None | None | None | None | N | None | 0 | 4.47748E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs760582847 |
-1.953 | 0.495 | N | 0.578 | 0.348 | 0.524166996187 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 8.28E-05 | 0 | None | 0 | 1.54258E-04 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs760582847 |
-1.953 | 0.495 | N | 0.578 | 0.348 | 0.524166996187 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs760582847 |
-1.953 | 0.495 | N | 0.578 | 0.348 | 0.524166996187 | gnomAD-4.0.0 | 8.06297E-06 | None | None | None | None | N | None | 4.00984E-05 | 0 | None | 0 | 1.33947E-04 | None | 0 | 1.64853E-04 | 1.69646E-06 | 1.09958E-05 | 0 |
| M/V | rs2057205184 |
None | 0.004 | N | 0.081 | 0.17 | 0.337868961071 | gnomAD-4.0.0 | 6.84764E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52118E-05 | None | 0 | 0 | 0 | 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 | 0.5161 | ambiguous | 0.5212 | ambiguous | -1.813 | Destabilizing | 0.362 | N | 0.531 | neutral | None | None | None | None | N |
| M/C | 0.6505 | likely_pathogenic | 0.6546 | pathogenic | -2.292 | Highly Destabilizing | 0.986 | D | 0.554 | neutral | None | None | None | None | N |
| M/D | 0.9824 | likely_pathogenic | 0.9849 | pathogenic | -2.195 | Highly Destabilizing | 0.986 | D | 0.727 | deleterious | None | None | None | None | N |
| M/E | 0.9361 | likely_pathogenic | 0.94 | pathogenic | -1.997 | Destabilizing | 0.951 | D | 0.597 | neutral | None | None | None | None | N |
| M/F | 0.5574 | ambiguous | 0.5762 | pathogenic | -0.477 | Destabilizing | 0.864 | D | 0.563 | neutral | None | None | None | None | N |
| M/G | 0.852 | likely_pathogenic | 0.8679 | pathogenic | -2.235 | Highly Destabilizing | 0.951 | D | 0.691 | prob.delet. | None | None | None | None | N |
| M/H | 0.9056 | likely_pathogenic | 0.9206 | pathogenic | -1.963 | Destabilizing | 0.986 | D | 0.591 | neutral | None | None | None | None | N |
| M/I | 0.3776 | ambiguous | 0.4165 | ambiguous | -0.625 | Destabilizing | 0.013 | N | 0.092 | neutral | N | 0.398716187 | None | None | N |
| M/K | 0.7406 | likely_pathogenic | 0.7859 | pathogenic | -1.18 | Destabilizing | 0.936 | D | 0.608 | neutral | N | 0.470040141 | None | None | N |
| M/L | 0.1944 | likely_benign | 0.2492 | benign | -0.625 | Destabilizing | 0.085 | N | 0.176 | neutral | N | 0.383239935 | None | None | N |
| M/N | 0.8683 | likely_pathogenic | 0.8849 | pathogenic | -1.522 | Destabilizing | 0.986 | D | 0.664 | prob.neutral | None | None | None | None | N |
| M/P | 0.8352 | likely_pathogenic | 0.8393 | pathogenic | -1.002 | Destabilizing | 0.986 | D | 0.647 | neutral | None | None | None | None | N |
| M/Q | 0.711 | likely_pathogenic | 0.7209 | pathogenic | -1.28 | Destabilizing | 0.986 | D | 0.586 | neutral | None | None | None | None | N |
| M/R | 0.7125 | likely_pathogenic | 0.737 | pathogenic | -1.307 | Destabilizing | 0.981 | D | 0.63 | neutral | N | 0.46932237 | None | None | N |
| M/S | 0.6989 | likely_pathogenic | 0.726 | pathogenic | -1.999 | Destabilizing | 0.864 | D | 0.616 | neutral | None | None | None | None | N |
| M/T | 0.4576 | ambiguous | 0.4664 | ambiguous | -1.684 | Destabilizing | 0.495 | N | 0.578 | neutral | N | 0.435499055 | None | None | N |
| M/V | 0.0795 | likely_benign | 0.0893 | benign | -1.002 | Destabilizing | 0.004 | N | 0.081 | neutral | N | 0.371903932 | None | None | N |
| M/W | 0.9268 | likely_pathogenic | 0.9535 | pathogenic | -0.854 | Destabilizing | 0.996 | D | 0.518 | neutral | None | None | None | None | N |
| M/Y | 0.8678 | likely_pathogenic | 0.9043 | pathogenic | -0.742 | Destabilizing | 0.986 | D | 0.629 | 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.