Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3322 | 10189;10190;10191 | chr2:178764551;178764550;178764549 | chr2:179629278;179629277;179629276 |
| N2AB | 3322 | 10189;10190;10191 | chr2:178764551;178764550;178764549 | chr2:179629278;179629277;179629276 |
| N2A | 3322 | 10189;10190;10191 | chr2:178764551;178764550;178764549 | chr2:179629278;179629277;179629276 |
| N2B | 3276 | 10051;10052;10053 | chr2:178764551;178764550;178764549 | chr2:179629278;179629277;179629276 |
| Novex-1 | 3276 | 10051;10052;10053 | chr2:178764551;178764550;178764549 | chr2:179629278;179629277;179629276 |
| Novex-2 | 3276 | 10051;10052;10053 | chr2:178764551;178764550;178764549 | chr2:179629278;179629277;179629276 |
| Novex-3 | 3322 | 10189;10190;10191 | chr2:178764551;178764550;178764549 | chr2:179629278;179629277;179629276 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs750311932  |
-1.138 | 0.454 | N | 0.52 | 0.207 | 0.250039746154 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| T/A | rs750311932 |
-1.138 | 0.454 | N | 0.52 | 0.207 | 0.250039746154 | gnomAD-4.0.0 | 1.59057E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85647E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.098 | likely_benign | 0.1333 | benign | -0.951 | Destabilizing | 0.454 | N | 0.52 | neutral | N | 0.479655817 | None | None | N |
| T/C | 0.6495 | likely_pathogenic | 0.6581 | pathogenic | -0.55 | Destabilizing | 0.037 | N | 0.525 | neutral | None | None | None | None | N |
| T/D | 0.8069 | likely_pathogenic | 0.9054 | pathogenic | -0.437 | Destabilizing | 0.842 | D | 0.733 | prob.delet. | None | None | None | None | N |
| T/E | 0.7766 | likely_pathogenic | 0.9054 | pathogenic | -0.429 | Destabilizing | 0.842 | D | 0.732 | prob.delet. | None | None | None | None | N |
| T/F | 0.6828 | likely_pathogenic | 0.7736 | pathogenic | -1.037 | Destabilizing | 0.991 | D | 0.757 | deleterious | None | None | None | None | N |
| T/G | 0.474 | ambiguous | 0.4925 | ambiguous | -1.216 | Destabilizing | 0.728 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/H | 0.6874 | likely_pathogenic | 0.7849 | pathogenic | -1.502 | Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | N |
| T/I | 0.4942 | ambiguous | 0.6216 | pathogenic | -0.328 | Destabilizing | 0.966 | D | 0.767 | deleterious | N | 0.509106312 | None | None | N |
| T/K | 0.7176 | likely_pathogenic | 0.8567 | pathogenic | -0.737 | Destabilizing | 0.801 | D | 0.728 | prob.delet. | N | 0.496223418 | None | None | N |
| T/L | 0.3448 | ambiguous | 0.3961 | ambiguous | -0.328 | Destabilizing | 0.842 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/M | 0.2472 | likely_benign | 0.2945 | benign | 0.077 | Stabilizing | 0.991 | D | 0.723 | prob.delet. | None | None | None | None | N |
| T/N | 0.4154 | ambiguous | 0.5449 | ambiguous | -0.702 | Destabilizing | 0.842 | D | 0.724 | prob.delet. | None | None | None | None | N |
| T/P | 0.7997 | likely_pathogenic | 0.8467 | pathogenic | -0.504 | Destabilizing | 0.966 | D | 0.759 | deleterious | D | 0.664984539 | None | None | N |
| T/Q | 0.6536 | likely_pathogenic | 0.7927 | pathogenic | -0.902 | Destabilizing | 0.974 | D | 0.749 | deleterious | None | None | None | None | N |
| T/R | 0.5842 | likely_pathogenic | 0.7654 | pathogenic | -0.498 | Destabilizing | 0.934 | D | 0.761 | deleterious | N | 0.506097657 | None | None | N |
| T/S | 0.1663 | likely_benign | 0.165 | benign | -0.996 | Destabilizing | 0.022 | N | 0.236 | neutral | N | 0.425039821 | None | None | N |
| T/V | 0.3042 | likely_benign | 0.3889 | ambiguous | -0.504 | Destabilizing | 0.842 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/W | 0.9441 | likely_pathogenic | 0.9643 | pathogenic | -0.939 | Destabilizing | 0.998 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/Y | 0.765 | likely_pathogenic | 0.8589 | pathogenic | -0.707 | Destabilizing | 0.991 | D | 0.737 | prob.delet. | 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.