Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24398 | 73417;73418;73419 | chr2:178572940;178572939;178572938 | chr2:179437667;179437666;179437665 |
| N2AB | 22757 | 68494;68495;68496 | chr2:178572940;178572939;178572938 | chr2:179437667;179437666;179437665 |
| N2A | 21830 | 65713;65714;65715 | chr2:178572940;178572939;178572938 | chr2:179437667;179437666;179437665 |
| N2B | 15333 | 46222;46223;46224 | chr2:178572940;178572939;178572938 | chr2:179437667;179437666;179437665 |
| Novex-1 | 15458 | 46597;46598;46599 | chr2:178572940;178572939;178572938 | chr2:179437667;179437666;179437665 |
| Novex-2 | 15525 | 46798;46799;46800 | chr2:178572940;178572939;178572938 | chr2:179437667;179437666;179437665 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs779146599  |
-1.64 | 0.998 | D | 0.727 | 0.461 | 0.794188585459 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| R/C | rs779146599 |
-1.64 | 0.998 | D | 0.727 | 0.461 | 0.794188585459 | gnomAD-4.0.0 | 1.30044E-05 | None | None | None | None | N | None | 0 | 0 | None | 3.82878E-05 | 0 | None | 1.87371E-05 | 1.73611E-04 | 1.34943E-05 | 0 | 1.65733E-05 |
| R/H | rs757790881 |
-2.077 | 0.021 | D | 0.409 | 0.379 | 0.284539287134 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.64E-05 | None | 0 | None | 0 | 0 | 0 |
| R/H | rs757790881 |
-2.077 | 0.021 | D | 0.409 | 0.379 | 0.284539287134 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs757790881 |
-2.077 | 0.021 | D | 0.409 | 0.379 | 0.284539287134 | gnomAD-4.0.0 | 6.19929E-06 | None | None | None | None | N | None | 6.67913E-05 | 0 | None | 0 | 6.71592E-05 | None | 0 | 0 | 8.47771E-07 | 0 | 1.6019E-05 |
| R/P | None | None | 0.985 | D | 0.643 | 0.499 | 0.563619085548 | gnomAD-4.0.0 | 6.84434E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99614E-07 | 0 | 0 |
| R/S | None | None | 0.39 | N | 0.549 | 0.404 | 0.422040124859 | gnomAD-4.0.0 | 6.84443E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9962E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6945 | likely_pathogenic | 0.6181 | pathogenic | -2.055 | Highly Destabilizing | 0.4 | N | 0.545 | neutral | None | None | None | None | N |
| R/C | 0.1854 | likely_benign | 0.1377 | benign | -1.934 | Destabilizing | 0.998 | D | 0.727 | prob.delet. | D | 0.551768884 | None | None | N |
| R/D | 0.9454 | likely_pathogenic | 0.9178 | pathogenic | -1.567 | Destabilizing | 0.447 | N | 0.579 | neutral | None | None | None | None | N |
| R/E | 0.7338 | likely_pathogenic | 0.6872 | pathogenic | -1.332 | Destabilizing | 0.4 | N | 0.532 | neutral | None | None | None | None | N |
| R/F | 0.8626 | likely_pathogenic | 0.7804 | pathogenic | -1.025 | Destabilizing | 0.85 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/G | 0.5886 | likely_pathogenic | 0.5265 | ambiguous | -2.389 | Highly Destabilizing | 0.39 | N | 0.557 | neutral | D | 0.551515394 | None | None | N |
| R/H | 0.1558 | likely_benign | 0.1176 | benign | -1.82 | Destabilizing | 0.021 | N | 0.409 | neutral | D | 0.551768884 | None | None | N |
| R/I | 0.6291 | likely_pathogenic | 0.5089 | ambiguous | -1.06 | Destabilizing | 0.92 | D | 0.68 | prob.neutral | None | None | None | None | N |
| R/K | 0.2149 | likely_benign | 0.1867 | benign | -1.193 | Destabilizing | 0.4 | N | 0.553 | neutral | None | None | None | None | N |
| R/L | 0.5471 | ambiguous | 0.4409 | ambiguous | -1.06 | Destabilizing | 0.756 | D | 0.551 | neutral | N | 0.506179078 | None | None | N |
| R/M | 0.6175 | likely_pathogenic | 0.5145 | ambiguous | -1.572 | Destabilizing | 0.972 | D | 0.643 | neutral | None | None | None | None | N |
| R/N | 0.7356 | likely_pathogenic | 0.6301 | pathogenic | -1.704 | Destabilizing | 0.001 | N | 0.211 | neutral | None | None | None | None | N |
| R/P | 0.993 | likely_pathogenic | 0.9911 | pathogenic | -1.386 | Destabilizing | 0.985 | D | 0.643 | neutral | D | 0.552022374 | None | None | N |
| R/Q | 0.14 | likely_benign | 0.1246 | benign | -1.43 | Destabilizing | 0.617 | D | 0.576 | neutral | None | None | None | None | N |
| R/S | 0.715 | likely_pathogenic | 0.6215 | pathogenic | -2.41 | Highly Destabilizing | 0.39 | N | 0.549 | neutral | N | 0.510365679 | None | None | N |
| R/T | 0.6477 | likely_pathogenic | 0.5477 | ambiguous | -1.971 | Destabilizing | 0.617 | D | 0.549 | neutral | None | None | None | None | N |
| R/V | 0.6838 | likely_pathogenic | 0.587 | pathogenic | -1.386 | Destabilizing | 0.92 | D | 0.636 | neutral | None | None | None | None | N |
| R/W | 0.5051 | ambiguous | 0.4011 | ambiguous | -0.617 | Destabilizing | 0.992 | D | 0.755 | deleterious | None | None | None | None | N |
| R/Y | 0.6584 | likely_pathogenic | 0.535 | ambiguous | -0.559 | Destabilizing | 0.739 | D | 0.637 | 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.