Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28196 | 84811;84812;84813 | chr2:178561546;178561545;178561544 | chr2:179426273;179426272;179426271 |
| N2AB | 26555 | 79888;79889;79890 | chr2:178561546;178561545;178561544 | chr2:179426273;179426272;179426271 |
| N2A | 25628 | 77107;77108;77109 | chr2:178561546;178561545;178561544 | chr2:179426273;179426272;179426271 |
| N2B | 19131 | 57616;57617;57618 | chr2:178561546;178561545;178561544 | chr2:179426273;179426272;179426271 |
| Novex-1 | 19256 | 57991;57992;57993 | chr2:178561546;178561545;178561544 | chr2:179426273;179426272;179426271 |
| Novex-2 | 19323 | 58192;58193;58194 | chr2:178561546;178561545;178561544 | chr2:179426273;179426272;179426271 |
| 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/S | rs773466308  |
-0.056 | 0.684 | N | 0.407 | 0.214 | 0.249502417897 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| R/S | rs773466308 |
-0.056 | 0.684 | N | 0.407 | 0.214 | 0.249502417897 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.0289E-04 | 0 | 0 |
| R/S | rs773466308 |
-0.056 | 0.684 | N | 0.407 | 0.214 | 0.249502417897 | gnomAD-4.0.0 | 1.67369E-05 | None | None | None | None | N | None | 2.66994E-05 | 1.66845E-05 | None | 0 | 0 | None | 0 | 0 | 1.86516E-05 | 0 | 3.20318E-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 | 0.6855 | likely_pathogenic | 0.7016 | pathogenic | -0.502 | Destabilizing | 0.373 | N | 0.423 | neutral | None | None | None | None | N |
| R/C | 0.3299 | likely_benign | 0.337 | benign | -0.337 | Destabilizing | 0.996 | D | 0.518 | neutral | None | None | None | None | N |
| R/D | 0.9125 | likely_pathogenic | 0.9166 | pathogenic | -0.013 | Destabilizing | 0.742 | D | 0.504 | neutral | None | None | None | None | N |
| R/E | 0.6862 | likely_pathogenic | 0.693 | pathogenic | 0.087 | Stabilizing | 0.373 | N | 0.397 | neutral | None | None | None | None | N |
| R/F | 0.8305 | likely_pathogenic | 0.839 | pathogenic | -0.501 | Destabilizing | 0.984 | D | 0.498 | neutral | None | None | None | None | N |
| R/G | 0.554 | ambiguous | 0.566 | pathogenic | -0.784 | Destabilizing | 0.684 | D | 0.481 | neutral | N | 0.476152177 | None | None | N |
| R/H | 0.2138 | likely_benign | 0.2076 | benign | -1.271 | Destabilizing | 0.953 | D | 0.424 | neutral | None | None | None | None | N |
| R/I | 0.4902 | ambiguous | 0.5092 | ambiguous | 0.237 | Stabilizing | 0.939 | D | 0.509 | neutral | N | 0.48280879 | None | None | N |
| R/K | 0.1464 | likely_benign | 0.1369 | benign | -0.498 | Destabilizing | 0.003 | N | 0.224 | neutral | N | 0.398651398 | None | None | N |
| R/L | 0.4753 | ambiguous | 0.4931 | ambiguous | 0.237 | Stabilizing | 0.742 | D | 0.481 | neutral | None | None | None | None | N |
| R/M | 0.5466 | ambiguous | 0.5527 | ambiguous | -0.029 | Destabilizing | 0.984 | D | 0.453 | neutral | None | None | None | None | N |
| R/N | 0.8246 | likely_pathogenic | 0.8364 | pathogenic | 0.049 | Stabilizing | 0.742 | D | 0.387 | neutral | None | None | None | None | N |
| R/P | 0.8125 | likely_pathogenic | 0.8499 | pathogenic | 0.012 | Stabilizing | 0.953 | D | 0.486 | neutral | None | None | None | None | N |
| R/Q | 0.1673 | likely_benign | 0.159 | benign | -0.136 | Destabilizing | 0.045 | N | 0.21 | neutral | None | None | None | None | N |
| R/S | 0.8033 | likely_pathogenic | 0.8115 | pathogenic | -0.594 | Destabilizing | 0.684 | D | 0.407 | neutral | N | 0.470898286 | None | None | N |
| R/T | 0.6101 | likely_pathogenic | 0.6202 | pathogenic | -0.325 | Destabilizing | 0.684 | D | 0.417 | neutral | N | 0.476746822 | None | None | N |
| R/V | 0.584 | likely_pathogenic | 0.6018 | pathogenic | 0.012 | Stabilizing | 0.742 | D | 0.494 | neutral | None | None | None | None | N |
| R/W | 0.414 | ambiguous | 0.4197 | ambiguous | -0.286 | Destabilizing | 0.996 | D | 0.535 | neutral | None | None | None | None | N |
| R/Y | 0.6386 | likely_pathogenic | 0.6456 | pathogenic | 0.052 | Stabilizing | 0.984 | D | 0.502 | 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.