Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30490 | 91693;91694;91695 | chr2:178551063;178551062;178551061 | chr2:179415790;179415789;179415788 |
| N2AB | 28849 | 86770;86771;86772 | chr2:178551063;178551062;178551061 | chr2:179415790;179415789;179415788 |
| N2A | 27922 | 83989;83990;83991 | chr2:178551063;178551062;178551061 | chr2:179415790;179415789;179415788 |
| N2B | 21425 | 64498;64499;64500 | chr2:178551063;178551062;178551061 | chr2:179415790;179415789;179415788 |
| Novex-1 | 21550 | 64873;64874;64875 | chr2:178551063;178551062;178551061 | chr2:179415790;179415789;179415788 |
| Novex-2 | 21617 | 65074;65075;65076 | chr2:178551063;178551062;178551061 | chr2:179415790;179415789;179415788 |
| 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/G | rs750498415  |
-1.355 | 1.0 | N | 0.722 | 0.499 | 0.265929055128 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.55E-05 | None | 0 | 8.91E-06 | 0 |
| D/G | rs750498415 |
-1.355 | 1.0 | N | 0.722 | 0.499 | 0.265929055128 | gnomAD-4.0.0 | 1.2739E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85971E-06 | 1.00353E-04 | 0 |
| D/N | rs758532843 |
-1.078 | 1.0 | N | 0.607 | 0.389 | 0.263140351381 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| D/N | rs758532843 |
-1.078 | 1.0 | N | 0.607 | 0.389 | 0.263140351381 | gnomAD-4.0.0 | 1.36885E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99625E-07 | 0 | 1.6575E-05 |
| D/Y | rs758532843 |
-0.211 | 1.0 | N | 0.727 | 0.46 | 0.642398420904 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| D/Y | rs758532843 |
-0.211 | 1.0 | N | 0.727 | 0.46 | 0.642398420904 | gnomAD-4.0.0 | 8.8975E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.16951E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2369 | likely_benign | 0.3235 | benign | -0.674 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | N | 0.38364466 | None | None | N |
| D/C | 0.6428 | likely_pathogenic | 0.7352 | pathogenic | -0.332 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/E | 0.1613 | likely_benign | 0.1885 | benign | -0.74 | Destabilizing | 1.0 | D | 0.457 | neutral | N | 0.39961419 | None | None | N |
| D/F | 0.65 | likely_pathogenic | 0.7535 | pathogenic | -0.231 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| D/G | 0.2661 | likely_benign | 0.3577 | ambiguous | -1.032 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.445175909 | None | None | N |
| D/H | 0.4216 | ambiguous | 0.5346 | ambiguous | -0.585 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.443925115 | None | None | N |
| D/I | 0.5145 | ambiguous | 0.6377 | pathogenic | 0.278 | Stabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/K | 0.5693 | likely_pathogenic | 0.6725 | pathogenic | -0.644 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| D/L | 0.4886 | ambiguous | 0.6021 | pathogenic | 0.278 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/M | 0.6215 | likely_pathogenic | 0.7241 | pathogenic | 0.783 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| D/N | 0.1305 | likely_benign | 0.1712 | benign | -1.063 | Destabilizing | 1.0 | D | 0.607 | neutral | N | 0.441962245 | None | None | N |
| D/P | 0.9682 | likely_pathogenic | 0.9807 | pathogenic | -0.014 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| D/Q | 0.363 | ambiguous | 0.4542 | ambiguous | -0.899 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| D/R | 0.6372 | likely_pathogenic | 0.7363 | pathogenic | -0.435 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| D/S | 0.1552 | likely_benign | 0.2076 | benign | -1.321 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| D/T | 0.3768 | ambiguous | 0.485 | ambiguous | -1.029 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/V | 0.3436 | ambiguous | 0.4555 | ambiguous | -0.014 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | N | 0.412082055 | None | None | N |
| D/W | 0.9205 | likely_pathogenic | 0.9495 | pathogenic | -0.046 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/Y | 0.3183 | likely_benign | 0.4091 | ambiguous | -0.015 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | N | 0.472178479 | 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.