Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14484 | 43675;43676;43677 | chr2:178632556;178632555;178632554 | chr2:179497283;179497282;179497281 |
| N2AB | 12843 | 38752;38753;38754 | chr2:178632556;178632555;178632554 | chr2:179497283;179497282;179497281 |
| N2A | 11916 | 35971;35972;35973 | chr2:178632556;178632555;178632554 | chr2:179497283;179497282;179497281 |
| N2B | 5419 | 16480;16481;16482 | chr2:178632556;178632555;178632554 | chr2:179497283;179497282;179497281 |
| Novex-1 | 5544 | 16855;16856;16857 | chr2:178632556;178632555;178632554 | chr2:179497283;179497282;179497281 |
| Novex-2 | 5611 | 17056;17057;17058 | chr2:178632556;178632555;178632554 | chr2:179497283;179497282;179497281 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs762264832  |
-0.092 | 0.201 | D | 0.502 | 0.217 | 0.298745278005 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.14E-05 | 0 |
| K/E | rs762264832 |
-0.092 | 0.201 | D | 0.502 | 0.217 | 0.298745278005 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/E | rs762264832 |
-0.092 | 0.201 | D | 0.502 | 0.217 | 0.298745278005 | gnomAD-4.0.0 | 6.19865E-06 | None | None | None | None | N | None | 4.00545E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.2388E-06 | 0 | 3.2039E-05 |
| K/N | None | None | 0.015 | N | 0.267 | 0.105 | 0.144782658237 | gnomAD-4.0.0 | 4.79094E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29742E-06 | 0 | 0 |
| K/Q | None | None | 0.004 | N | 0.236 | 0.153 | 0.184867976434 | gnomAD-4.0.0 | 6.8441E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9963E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.5497 | ambiguous | 0.5269 | ambiguous | -0.61 | Destabilizing | 0.25 | N | 0.501 | neutral | None | None | None | None | N |
| K/C | 0.8163 | likely_pathogenic | 0.8022 | pathogenic | -0.498 | Destabilizing | 0.982 | D | 0.741 | deleterious | None | None | None | None | N |
| K/D | 0.8132 | likely_pathogenic | 0.7844 | pathogenic | -0.375 | Destabilizing | 0.25 | N | 0.535 | neutral | None | None | None | None | N |
| K/E | 0.3281 | likely_benign | 0.292 | benign | -0.217 | Destabilizing | 0.201 | N | 0.502 | neutral | D | 0.560043169 | None | None | N |
| K/F | 0.8755 | likely_pathogenic | 0.8544 | pathogenic | -0.051 | Destabilizing | 0.935 | D | 0.714 | prob.delet. | None | None | None | None | N |
| K/G | 0.6748 | likely_pathogenic | 0.6479 | pathogenic | -1.017 | Destabilizing | 0.399 | N | 0.557 | neutral | None | None | None | None | N |
| K/H | 0.4533 | ambiguous | 0.4042 | ambiguous | -1.282 | Destabilizing | 0.7 | D | 0.63 | neutral | None | None | None | None | N |
| K/I | 0.4662 | ambiguous | 0.4695 | ambiguous | 0.469 | Stabilizing | 0.826 | D | 0.72 | prob.delet. | None | None | None | None | N |
| K/L | 0.5486 | ambiguous | 0.5168 | ambiguous | 0.469 | Stabilizing | 0.7 | D | 0.572 | neutral | None | None | None | None | N |
| K/M | 0.344 | ambiguous | 0.3296 | benign | 0.164 | Stabilizing | 0.931 | D | 0.614 | neutral | D | 0.547497417 | None | None | N |
| K/N | 0.5646 | likely_pathogenic | 0.512 | ambiguous | -0.662 | Destabilizing | 0.015 | N | 0.267 | neutral | N | 0.507975221 | None | None | N |
| K/P | 0.9552 | likely_pathogenic | 0.9578 | pathogenic | 0.138 | Stabilizing | 0.826 | D | 0.619 | neutral | None | None | None | None | N |
| K/Q | 0.1866 | likely_benign | 0.1632 | benign | -0.565 | Destabilizing | 0.004 | N | 0.236 | neutral | N | 0.513305208 | None | None | N |
| K/R | 0.1048 | likely_benign | 0.1052 | benign | -0.766 | Destabilizing | 0.201 | N | 0.485 | neutral | N | 0.510398081 | None | None | N |
| K/S | 0.5732 | likely_pathogenic | 0.5313 | ambiguous | -1.19 | Destabilizing | 0.25 | N | 0.485 | neutral | None | None | None | None | N |
| K/T | 0.2781 | likely_benign | 0.2608 | benign | -0.816 | Destabilizing | 0.334 | N | 0.547 | neutral | N | 0.512483151 | None | None | N |
| K/V | 0.4765 | ambiguous | 0.4781 | ambiguous | 0.138 | Stabilizing | 0.7 | D | 0.59 | neutral | None | None | None | None | N |
| K/W | 0.8892 | likely_pathogenic | 0.8716 | pathogenic | -0.021 | Destabilizing | 0.982 | D | 0.715 | prob.delet. | None | None | None | None | N |
| K/Y | 0.7607 | likely_pathogenic | 0.7127 | pathogenic | 0.238 | Stabilizing | 0.826 | D | 0.687 | prob.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.