Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15980 | 48163;48164;48165 | chr2:178616951;178616950;178616949 | chr2:179481678;179481677;179481676 |
| N2AB | 14339 | 43240;43241;43242 | chr2:178616951;178616950;178616949 | chr2:179481678;179481677;179481676 |
| N2A | 13412 | 40459;40460;40461 | chr2:178616951;178616950;178616949 | chr2:179481678;179481677;179481676 |
| N2B | 6915 | 20968;20969;20970 | chr2:178616951;178616950;178616949 | chr2:179481678;179481677;179481676 |
| Novex-1 | 7040 | 21343;21344;21345 | chr2:178616951;178616950;178616949 | chr2:179481678;179481677;179481676 |
| Novex-2 | 7107 | 21544;21545;21546 | chr2:178616951;178616950;178616949 | chr2:179481678;179481677;179481676 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | None | None | 0.989 | N | 0.719 | 0.437 | 0.70846858115 | gnomAD-4.0.0 | 1.59336E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86267E-06 | 0 | 0 |
| I/T | rs1299741531  |
-2.322 | 0.891 | N | 0.653 | 0.283 | 0.545432718849 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1299741531 |
-2.322 | 0.891 | N | 0.653 | 0.283 | 0.545432718849 | gnomAD-4.0.0 | 3.18672E-06 | None | None | None | None | N | None | 0 | 4.57582E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs780634456 |
-0.707 | 0.267 | N | 0.405 | 0.053 | 0.233785782151 | gnomAD-2.1.1 | 6.05E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.92182E-04 | None | 0 | 1.79E-05 | 1.66279E-04 |
| I/V | rs780634456 |
-0.707 | 0.267 | N | 0.405 | 0.053 | 0.233785782151 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 2.07383E-04 | 0 |
| I/V | rs780634456 |
-0.707 | 0.267 | N | 0.405 | 0.053 | 0.233785782151 | gnomAD-4.0.0 | 2.66651E-05 | None | None | None | None | N | None | 0 | 1.66889E-05 | None | 0 | 0 | None | 0 | 4.94234E-04 | 1.18733E-05 | 2.52608E-04 | 3.20554E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8868 | likely_pathogenic | 0.9051 | pathogenic | -2.831 | Highly Destabilizing | 0.688 | D | 0.651 | neutral | None | None | None | None | N |
| I/C | 0.9413 | likely_pathogenic | 0.9489 | pathogenic | -2.196 | Highly Destabilizing | 0.998 | D | 0.664 | neutral | None | None | None | None | N |
| I/D | 0.997 | likely_pathogenic | 0.9978 | pathogenic | -3.235 | Highly Destabilizing | 0.991 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/E | 0.9907 | likely_pathogenic | 0.9934 | pathogenic | -2.933 | Highly Destabilizing | 0.991 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/F | 0.7288 | likely_pathogenic | 0.6869 | pathogenic | -1.699 | Destabilizing | 0.934 | D | 0.695 | prob.neutral | N | 0.454156639 | None | None | N |
| I/G | 0.9881 | likely_pathogenic | 0.9909 | pathogenic | -3.457 | Highly Destabilizing | 0.991 | D | 0.686 | prob.neutral | None | None | None | None | N |
| I/H | 0.9906 | likely_pathogenic | 0.9929 | pathogenic | -2.967 | Highly Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | N |
| I/K | 0.9773 | likely_pathogenic | 0.9843 | pathogenic | -2.335 | Highly Destabilizing | 0.974 | D | 0.683 | prob.neutral | None | None | None | None | N |
| I/L | 0.1175 | likely_benign | 0.1443 | benign | -0.978 | Destabilizing | 0.002 | N | 0.283 | neutral | N | 0.403330671 | None | None | N |
| I/M | 0.2427 | likely_benign | 0.2481 | benign | -1.022 | Destabilizing | 0.934 | D | 0.701 | prob.neutral | N | 0.513674237 | None | None | N |
| I/N | 0.9684 | likely_pathogenic | 0.9783 | pathogenic | -2.908 | Highly Destabilizing | 0.989 | D | 0.719 | prob.delet. | N | 0.514733762 | None | None | N |
| I/P | 0.99 | likely_pathogenic | 0.9929 | pathogenic | -1.581 | Destabilizing | 0.991 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/Q | 0.9805 | likely_pathogenic | 0.985 | pathogenic | -2.622 | Highly Destabilizing | 0.991 | D | 0.718 | prob.delet. | None | None | None | None | N |
| I/R | 0.9695 | likely_pathogenic | 0.9781 | pathogenic | -2.205 | Highly Destabilizing | 0.974 | D | 0.714 | prob.delet. | None | None | None | None | N |
| I/S | 0.9644 | likely_pathogenic | 0.9711 | pathogenic | -3.623 | Highly Destabilizing | 0.966 | D | 0.653 | neutral | N | 0.474573549 | None | None | N |
| I/T | 0.9326 | likely_pathogenic | 0.9509 | pathogenic | -3.147 | Highly Destabilizing | 0.891 | D | 0.653 | neutral | N | 0.443634916 | None | None | N |
| I/V | 0.1063 | likely_benign | 0.1139 | benign | -1.581 | Destabilizing | 0.267 | N | 0.405 | neutral | N | 0.436545968 | None | None | N |
| I/W | 0.9942 | likely_pathogenic | 0.9937 | pathogenic | -2.096 | Highly Destabilizing | 0.998 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/Y | 0.9705 | likely_pathogenic | 0.9711 | pathogenic | -1.832 | Destabilizing | 0.974 | D | 0.697 | prob.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.