Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22535 | 67828;67829;67830 | chr2:178579594;178579593;178579592 | chr2:179444321;179444320;179444319 |
| N2AB | 20894 | 62905;62906;62907 | chr2:178579594;178579593;178579592 | chr2:179444321;179444320;179444319 |
| N2A | 19967 | 60124;60125;60126 | chr2:178579594;178579593;178579592 | chr2:179444321;179444320;179444319 |
| N2B | 13470 | 40633;40634;40635 | chr2:178579594;178579593;178579592 | chr2:179444321;179444320;179444319 |
| Novex-1 | 13595 | 41008;41009;41010 | chr2:178579594;178579593;178579592 | chr2:179444321;179444320;179444319 |
| Novex-2 | 13662 | 41209;41210;41211 | chr2:178579594;178579593;178579592 | chr2:179444321;179444320;179444319 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs375676529  |
-0.862 | 0.351 | D | 0.689 | 0.288 | None | gnomAD-2.1.1 | 7.88E-05 | None | None | None | None | N | None | 1.24059E-04 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 8E-05 | 1.17978E-04 | 0 |
| S/N | rs375676529 |
-0.862 | 0.351 | D | 0.689 | 0.288 | None | gnomAD-3.1.2 | 1.24969E-04 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 1.88573E-04 | 0 | 1.91221E-04 | 0 | 0 |
| S/N | rs375676529 |
-0.862 | 0.351 | D | 0.689 | 0.288 | None | gnomAD-4.0.0 | 1.20259E-04 | None | None | None | None | N | None | 9.34979E-05 | 0 | None | 0 | 0 | None | 3.12705E-05 | 0 | 1.49215E-04 | 0 | 1.44143E-04 |
| S/R | rs750847940 |
-0.536 | 0.002 | N | 0.512 | 0.414 | 0.152612264143 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| S/R | rs750847940 |
-0.536 | 0.002 | N | 0.512 | 0.414 | 0.152612264143 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs750847940 |
-0.536 | 0.002 | N | 0.512 | 0.414 | 0.152612264143 | gnomAD-4.0.0 | 6.84406E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99669E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0798 | likely_benign | 0.0802 | benign | -0.682 | Destabilizing | 0.061 | N | 0.571 | neutral | None | None | None | None | N |
| S/C | 0.0878 | likely_benign | 0.0938 | benign | -0.558 | Destabilizing | 0.978 | D | 0.767 | deleterious | D | 0.54138249 | None | None | N |
| S/D | 0.4156 | ambiguous | 0.5245 | ambiguous | -0.209 | Destabilizing | 0.418 | N | 0.663 | neutral | None | None | None | None | N |
| S/E | 0.4343 | ambiguous | 0.5264 | ambiguous | -0.191 | Destabilizing | 0.418 | N | 0.649 | neutral | None | None | None | None | N |
| S/F | 0.2643 | likely_benign | 0.3076 | benign | -0.711 | Destabilizing | 0.836 | D | 0.811 | deleterious | None | None | None | None | N |
| S/G | 0.0977 | likely_benign | 0.1111 | benign | -0.957 | Destabilizing | 0.183 | N | 0.641 | neutral | N | 0.510400992 | None | None | N |
| S/H | 0.3127 | likely_benign | 0.3843 | ambiguous | -1.39 | Destabilizing | 0.836 | D | 0.769 | deleterious | None | None | None | None | N |
| S/I | 0.156 | likely_benign | 0.1943 | benign | -0.052 | Destabilizing | 0.007 | N | 0.627 | neutral | D | 0.52293584 | None | None | N |
| S/K | 0.4596 | ambiguous | 0.602 | pathogenic | -0.729 | Destabilizing | 0.129 | N | 0.638 | neutral | None | None | None | None | N |
| S/L | 0.1198 | likely_benign | 0.1257 | benign | -0.052 | Destabilizing | 0.129 | N | 0.696 | prob.neutral | None | None | None | None | N |
| S/M | 0.1925 | likely_benign | 0.2131 | benign | 0.066 | Stabilizing | 0.836 | D | 0.767 | deleterious | None | None | None | None | N |
| S/N | 0.1273 | likely_benign | 0.1678 | benign | -0.711 | Destabilizing | 0.351 | N | 0.689 | prob.neutral | D | 0.540622021 | None | None | N |
| S/P | 0.8319 | likely_pathogenic | 0.8684 | pathogenic | -0.227 | Destabilizing | 0.836 | D | 0.767 | deleterious | None | None | None | None | N |
| S/Q | 0.3752 | ambiguous | 0.4547 | ambiguous | -0.806 | Destabilizing | 0.716 | D | 0.705 | prob.neutral | None | None | None | None | N |
| S/R | 0.3539 | ambiguous | 0.4919 | ambiguous | -0.688 | Destabilizing | 0.002 | N | 0.512 | neutral | N | 0.521921882 | None | None | N |
| S/T | 0.0745 | likely_benign | 0.0748 | benign | -0.71 | Destabilizing | None | N | 0.357 | neutral | D | 0.537294715 | None | None | N |
| S/V | 0.1387 | likely_benign | 0.1549 | benign | -0.227 | Destabilizing | 0.129 | N | 0.708 | prob.delet. | None | None | None | None | N |
| S/W | 0.3984 | ambiguous | 0.4733 | ambiguous | -0.701 | Destabilizing | 0.983 | D | 0.831 | deleterious | None | None | None | None | N |
| S/Y | 0.211 | likely_benign | 0.2557 | benign | -0.432 | Destabilizing | 0.94 | D | 0.814 | deleterious | 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.