Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16086 | 48481;48482;48483 | chr2:178616535;178616534;178616533 | chr2:179481262;179481261;179481260 |
| N2AB | 14445 | 43558;43559;43560 | chr2:178616535;178616534;178616533 | chr2:179481262;179481261;179481260 |
| N2A | 13518 | 40777;40778;40779 | chr2:178616535;178616534;178616533 | chr2:179481262;179481261;179481260 |
| N2B | 7021 | 21286;21287;21288 | chr2:178616535;178616534;178616533 | chr2:179481262;179481261;179481260 |
| Novex-1 | 7146 | 21661;21662;21663 | chr2:178616535;178616534;178616533 | chr2:179481262;179481261;179481260 |
| Novex-2 | 7213 | 21862;21863;21864 | chr2:178616535;178616534;178616533 | chr2:179481262;179481261;179481260 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs567496224  |
-0.02 | 1.0 | D | 0.724 | 0.446 | 0.665643713772 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| P/L | rs567496224 |
-0.02 | 1.0 | D | 0.724 | 0.446 | 0.665643713772 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 0 | 6.58E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs567496224 |
-0.02 | 1.0 | D | 0.724 | 0.446 | 0.665643713772 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/L | rs567496224 |
-0.02 | 1.0 | D | 0.724 | 0.446 | 0.665643713772 | gnomAD-4.0.0 | 2.17098E-05 | None | None | None | None | I | None | 0 | 3.33934E-05 | None | 0 | 0 | None | 0 | 0 | 2.54473E-05 | 1.09895E-05 | 3.20585E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0901 | likely_benign | 0.1115 | benign | -0.43 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.521406272 | None | None | I |
| P/C | 0.4992 | ambiguous | 0.6757 | pathogenic | -0.541 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| P/D | 0.4234 | ambiguous | 0.5194 | ambiguous | -0.076 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| P/E | 0.2402 | likely_benign | 0.2874 | benign | -0.195 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| P/F | 0.4975 | ambiguous | 0.6204 | pathogenic | -0.731 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | I |
| P/G | 0.3736 | ambiguous | 0.4823 | ambiguous | -0.558 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| P/H | 0.2153 | likely_benign | 0.297 | benign | -0.194 | Destabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| P/I | 0.2632 | likely_benign | 0.3411 | ambiguous | -0.249 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| P/K | 0.26 | likely_benign | 0.3517 | ambiguous | -0.249 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| P/L | 0.1176 | likely_benign | 0.1566 | benign | -0.249 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | D | 0.669813395 | None | None | I |
| P/M | 0.2976 | likely_benign | 0.3788 | ambiguous | -0.198 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| P/N | 0.3518 | ambiguous | 0.4584 | ambiguous | 0.025 | Stabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| P/Q | 0.1569 | likely_benign | 0.2025 | benign | -0.23 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | D | 0.554700529 | None | None | I |
| P/R | 0.1886 | likely_benign | 0.2597 | benign | 0.229 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | D | 0.585964392 | None | None | I |
| P/S | 0.1407 | likely_benign | 0.1834 | benign | -0.374 | Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.556400062 | None | None | I |
| P/T | 0.1238 | likely_benign | 0.163 | benign | -0.389 | Destabilizing | 1.0 | D | 0.748 | deleterious | D | 0.587774265 | None | None | I |
| P/V | 0.1765 | likely_benign | 0.2283 | benign | -0.274 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| P/W | 0.715 | likely_pathogenic | 0.827 | pathogenic | -0.803 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| P/Y | 0.4754 | ambiguous | 0.5917 | pathogenic | -0.477 | Destabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | I |
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.