Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27130 | 81613;81614;81615 | chr2:178564744;178564743;178564742 | chr2:179429471;179429470;179429469 |
| N2AB | 25489 | 76690;76691;76692 | chr2:178564744;178564743;178564742 | chr2:179429471;179429470;179429469 |
| N2A | 24562 | 73909;73910;73911 | chr2:178564744;178564743;178564742 | chr2:179429471;179429470;179429469 |
| N2B | 18065 | 54418;54419;54420 | chr2:178564744;178564743;178564742 | chr2:179429471;179429470;179429469 |
| Novex-1 | 18190 | 54793;54794;54795 | chr2:178564744;178564743;178564742 | chr2:179429471;179429470;179429469 |
| Novex-2 | 18257 | 54994;54995;54996 | chr2:178564744;178564743;178564742 | chr2:179429471;179429470;179429469 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1458266524  |
-0.748 | 0.058 | N | 0.281 | 0.176 | 0.144782658237 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| T/A | rs1458266524 |
-0.748 | 0.058 | N | 0.281 | 0.176 | 0.144782658237 | gnomAD-4.0.0 | 3.18701E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72253E-06 | 0 | 0 |
| T/I | rs757768218 |
0.329 | 0.698 | N | 0.485 | 0.421 | 0.425148423609 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| T/I | rs757768218 |
0.329 | 0.698 | N | 0.485 | 0.421 | 0.425148423609 | gnomAD-4.0.0 | 6.16132E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59899E-06 | 0 | 8.2905E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1357 | likely_benign | 0.1311 | benign | -0.7 | Destabilizing | 0.058 | N | 0.281 | neutral | N | 0.48724454 | None | None | N |
| T/C | 0.2615 | likely_benign | 0.255 | benign | -0.427 | Destabilizing | 0.043 | N | 0.364 | neutral | None | None | None | None | N |
| T/D | 0.6181 | likely_pathogenic | 0.604 | pathogenic | -0.928 | Destabilizing | 0.993 | D | 0.556 | neutral | None | None | None | None | N |
| T/E | 0.5325 | ambiguous | 0.5044 | ambiguous | -0.755 | Destabilizing | 0.978 | D | 0.546 | neutral | None | None | None | None | N |
| T/F | 0.532 | ambiguous | 0.5157 | ambiguous | -0.465 | Destabilizing | 0.956 | D | 0.617 | neutral | None | None | None | None | N |
| T/G | 0.2818 | likely_benign | 0.2754 | benign | -1.092 | Destabilizing | 0.86 | D | 0.523 | neutral | None | None | None | None | N |
| T/H | 0.3554 | ambiguous | 0.3524 | ambiguous | -1.273 | Destabilizing | 0.998 | D | 0.649 | neutral | None | None | None | None | N |
| T/I | 0.3915 | ambiguous | 0.3552 | ambiguous | 0.313 | Stabilizing | 0.698 | D | 0.485 | neutral | N | 0.50353837 | None | None | N |
| T/K | 0.1873 | likely_benign | 0.1722 | benign | -0.359 | Destabilizing | 0.978 | D | 0.536 | neutral | None | None | None | None | N |
| T/L | 0.1083 | likely_benign | 0.1017 | benign | 0.313 | Stabilizing | 0.019 | N | 0.352 | neutral | None | None | None | None | N |
| T/M | 0.1106 | likely_benign | 0.1099 | benign | 0.172 | Stabilizing | 0.956 | D | 0.588 | neutral | None | None | None | None | N |
| T/N | 0.1353 | likely_benign | 0.1304 | benign | -0.935 | Destabilizing | 0.99 | D | 0.534 | neutral | N | 0.481128474 | None | None | N |
| T/P | 0.2688 | likely_benign | 0.2668 | benign | 0.008 | Stabilizing | 0.99 | D | 0.565 | neutral | N | 0.486928599 | None | None | N |
| T/Q | 0.2508 | likely_benign | 0.2405 | benign | -0.717 | Destabilizing | 0.993 | D | 0.579 | neutral | None | None | None | None | N |
| T/R | 0.1449 | likely_benign | 0.1316 | benign | -0.545 | Destabilizing | 0.978 | D | 0.571 | neutral | None | None | None | None | N |
| T/S | 0.166 | likely_benign | 0.1662 | benign | -1.133 | Destabilizing | 0.698 | D | 0.497 | neutral | N | 0.490447318 | None | None | N |
| T/V | 0.2451 | likely_benign | 0.2214 | benign | 0.008 | Stabilizing | 0.754 | D | 0.481 | neutral | None | None | None | None | N |
| T/W | 0.8158 | likely_pathogenic | 0.8139 | pathogenic | -0.689 | Destabilizing | 0.998 | D | 0.678 | prob.neutral | None | None | None | None | N |
| T/Y | 0.4904 | ambiguous | 0.4842 | ambiguous | -0.259 | Destabilizing | 0.978 | D | 0.622 | 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.