Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27006 | 81241;81242;81243 | chr2:178565116;178565115;178565114 | chr2:179429843;179429842;179429841 |
| N2AB | 25365 | 76318;76319;76320 | chr2:178565116;178565115;178565114 | chr2:179429843;179429842;179429841 |
| N2A | 24438 | 73537;73538;73539 | chr2:178565116;178565115;178565114 | chr2:179429843;179429842;179429841 |
| N2B | 17941 | 54046;54047;54048 | chr2:178565116;178565115;178565114 | chr2:179429843;179429842;179429841 |
| Novex-1 | 18066 | 54421;54422;54423 | chr2:178565116;178565115;178565114 | chr2:179429843;179429842;179429841 |
| Novex-2 | 18133 | 54622;54623;54624 | chr2:178565116;178565115;178565114 | chr2:179429843;179429842;179429841 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/I | rs886055241  |
-0.115 | 0.007 | N | 0.253 | 0.22 | 0.456462010053 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| S/I | rs886055241 |
-0.115 | 0.007 | N | 0.253 | 0.22 | 0.456462010053 | gnomAD-4.0.0 | 1.59192E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85951E-06 | 0 | 0 |
| S/R | None | None | 0.884 | N | 0.383 | 0.302 | 0.419957187557 | gnomAD-4.0.0 | 3.18385E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43394E-05 | 3.02462E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1981 | likely_benign | 0.1782 | benign | -0.497 | Destabilizing | 0.543 | D | 0.403 | neutral | None | None | None | None | I |
| S/C | 0.2508 | likely_benign | 0.2283 | benign | -0.342 | Destabilizing | 0.994 | D | 0.404 | neutral | N | 0.487626615 | None | None | I |
| S/D | 0.8585 | likely_pathogenic | 0.8553 | pathogenic | -0.276 | Destabilizing | 0.59 | D | 0.275 | neutral | None | None | None | None | I |
| S/E | 0.9337 | likely_pathogenic | 0.943 | pathogenic | -0.355 | Destabilizing | 0.742 | D | 0.268 | neutral | None | None | None | None | I |
| S/F | 0.7193 | likely_pathogenic | 0.7103 | pathogenic | -0.976 | Destabilizing | 0.91 | D | 0.423 | neutral | None | None | None | None | I |
| S/G | 0.1743 | likely_benign | 0.1488 | benign | -0.644 | Destabilizing | 0.309 | N | 0.318 | neutral | N | 0.47124388 | None | None | I |
| S/H | 0.7244 | likely_pathogenic | 0.7375 | pathogenic | -1.189 | Destabilizing | 0.953 | D | 0.398 | neutral | None | None | None | None | I |
| S/I | 0.4761 | ambiguous | 0.5018 | ambiguous | -0.231 | Destabilizing | 0.007 | N | 0.253 | neutral | N | 0.502069341 | None | None | I |
| S/K | 0.9544 | likely_pathogenic | 0.9636 | pathogenic | -0.676 | Destabilizing | 0.742 | D | 0.269 | neutral | None | None | None | None | I |
| S/L | 0.2583 | likely_benign | 0.2612 | benign | -0.231 | Destabilizing | 0.17 | N | 0.375 | neutral | None | None | None | None | I |
| S/M | 0.394 | ambiguous | 0.3923 | ambiguous | 0.168 | Stabilizing | 0.91 | D | 0.398 | neutral | None | None | None | None | I |
| S/N | 0.1907 | likely_benign | 0.1712 | benign | -0.433 | Destabilizing | 0.001 | N | 0.081 | neutral | N | 0.456817054 | None | None | I |
| S/P | 0.8965 | likely_pathogenic | 0.897 | pathogenic | -0.29 | Destabilizing | 0.984 | D | 0.419 | neutral | None | None | None | None | I |
| S/Q | 0.8361 | likely_pathogenic | 0.8492 | pathogenic | -0.741 | Destabilizing | 0.953 | D | 0.381 | neutral | None | None | None | None | I |
| S/R | 0.9376 | likely_pathogenic | 0.9503 | pathogenic | -0.407 | Destabilizing | 0.884 | D | 0.383 | neutral | N | 0.504320213 | None | None | I |
| S/T | 0.1037 | likely_benign | 0.0985 | benign | -0.51 | Destabilizing | 0.472 | N | 0.343 | neutral | N | 0.400190194 | None | None | I |
| S/V | 0.4748 | ambiguous | 0.4778 | ambiguous | -0.29 | Destabilizing | 0.331 | N | 0.367 | neutral | None | None | None | None | I |
| S/W | 0.8275 | likely_pathogenic | 0.8349 | pathogenic | -0.944 | Destabilizing | 0.996 | D | 0.587 | neutral | None | None | None | None | I |
| S/Y | 0.6145 | likely_pathogenic | 0.6214 | pathogenic | -0.69 | Destabilizing | 0.953 | D | 0.417 | neutral | None | None | None | None | I |
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.