Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27216 | 81871;81872;81873 | chr2:178564486;178564485;178564484 | chr2:179429213;179429212;179429211 |
| N2AB | 25575 | 76948;76949;76950 | chr2:178564486;178564485;178564484 | chr2:179429213;179429212;179429211 |
| N2A | 24648 | 74167;74168;74169 | chr2:178564486;178564485;178564484 | chr2:179429213;179429212;179429211 |
| N2B | 18151 | 54676;54677;54678 | chr2:178564486;178564485;178564484 | chr2:179429213;179429212;179429211 |
| Novex-1 | 18276 | 55051;55052;55053 | chr2:178564486;178564485;178564484 | chr2:179429213;179429212;179429211 |
| Novex-2 | 18343 | 55252;55253;55254 | chr2:178564486;178564485;178564484 | chr2:179429213;179429212;179429211 |
| 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 | rs756815015  |
0.02 | 1.0 | N | 0.759 | 0.492 | 0.664980478371 | gnomAD-2.1.1 | 1.09E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.4E-05 | 0 |
| R/C | rs756815015 |
0.02 | 1.0 | N | 0.759 | 0.492 | 0.664980478371 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 4.78927E-04 |
| R/C | rs756815015 |
0.02 | 1.0 | N | 0.759 | 0.492 | 0.664980478371 | gnomAD-4.0.0 | 1.11676E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44213E-05 | 0 | 1.60287E-05 |
| R/H | rs371910831 |
-0.552 | 1.0 | N | 0.735 | 0.403 | None | gnomAD-2.1.1 | 3.27E-05 | None | None | None | None | N | None | 4.18E-05 | 2.87E-05 | None | 0 | 0 | None | 6.6E-05 | None | 0 | 3.2E-05 | 1.42857E-04 |
| R/H | rs371910831 |
-0.552 | 1.0 | N | 0.735 | 0.403 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 2.88184E-04 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 4.78469E-04 |
| R/H | rs371910831 |
-0.552 | 1.0 | N | 0.735 | 0.403 | None | gnomAD-4.0.0 | 2.544E-05 | None | None | None | None | N | None | 1.33526E-05 | 3.35132E-05 | None | 3.38226E-05 | 2.23954E-05 | None | 0 | 0 | 2.46026E-05 | 5.50176E-05 | 3.20646E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9388 | likely_pathogenic | 0.9388 | pathogenic | 0.178 | Stabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| R/C | 0.6315 | likely_pathogenic | 0.6072 | pathogenic | -0.013 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.484561969 | None | None | N |
| R/D | 0.972 | likely_pathogenic | 0.9713 | pathogenic | -0.198 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/E | 0.8897 | likely_pathogenic | 0.8854 | pathogenic | -0.136 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| R/F | 0.9293 | likely_pathogenic | 0.922 | pathogenic | -0.053 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/G | 0.8874 | likely_pathogenic | 0.877 | pathogenic | -0.002 | Destabilizing | 1.0 | D | 0.601 | neutral | N | 0.503221348 | None | None | N |
| R/H | 0.3467 | ambiguous | 0.3186 | benign | -0.59 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.468001423 | None | None | N |
| R/I | 0.8048 | likely_pathogenic | 0.8013 | pathogenic | 0.612 | Stabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/K | 0.3007 | likely_benign | 0.3045 | benign | 0.072 | Stabilizing | 0.998 | D | 0.615 | neutral | None | None | None | None | N |
| R/L | 0.775 | likely_pathogenic | 0.7673 | pathogenic | 0.612 | Stabilizing | 1.0 | D | 0.601 | neutral | N | 0.509822033 | None | None | N |
| R/M | 0.8512 | likely_pathogenic | 0.8525 | pathogenic | 0.076 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/N | 0.9415 | likely_pathogenic | 0.9422 | pathogenic | 0.218 | Stabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| R/P | 0.9447 | likely_pathogenic | 0.9433 | pathogenic | 0.487 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.4721028 | None | None | N |
| R/Q | 0.3835 | ambiguous | 0.3596 | ambiguous | 0.177 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/S | 0.9588 | likely_pathogenic | 0.9565 | pathogenic | 0.024 | Stabilizing | 1.0 | D | 0.625 | neutral | N | 0.482056642 | None | None | N |
| R/T | 0.8913 | likely_pathogenic | 0.8944 | pathogenic | 0.209 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| R/V | 0.8742 | likely_pathogenic | 0.8712 | pathogenic | 0.487 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/W | 0.6109 | likely_pathogenic | 0.5745 | pathogenic | -0.206 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| R/Y | 0.8095 | likely_pathogenic | 0.7964 | pathogenic | 0.211 | Stabilizing | 1.0 | D | 0.713 | 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.