Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22980 | 69163;69164;69165 | chr2:178577397;178577396;178577395 | chr2:179442124;179442123;179442122 |
| N2AB | 21339 | 64240;64241;64242 | chr2:178577397;178577396;178577395 | chr2:179442124;179442123;179442122 |
| N2A | 20412 | 61459;61460;61461 | chr2:178577397;178577396;178577395 | chr2:179442124;179442123;179442122 |
| N2B | 13915 | 41968;41969;41970 | chr2:178577397;178577396;178577395 | chr2:179442124;179442123;179442122 |
| Novex-1 | 14040 | 42343;42344;42345 | chr2:178577397;178577396;178577395 | chr2:179442124;179442123;179442122 |
| Novex-2 | 14107 | 42544;42545;42546 | chr2:178577397;178577396;178577395 | chr2:179442124;179442123;179442122 |
| 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/G | rs2046674740  |
None | None | N | 0.184 | 0.186 | 0.201204373187 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 6.58E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs2046674740 |
None | None | N | 0.184 | 0.186 | 0.201204373187 | gnomAD-4.0.0 | 2.56537E-06 | None | None | None | None | N | None | 0 | 1.69722E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 2.84722E-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 | 0.082 | likely_benign | 0.0809 | benign | -0.869 | Destabilizing | None | N | 0.179 | neutral | None | None | None | None | N |
| S/C | 0.0859 | likely_benign | 0.0814 | benign | -0.479 | Destabilizing | 0.196 | N | 0.478 | neutral | D | 0.539489658 | None | None | N |
| S/D | 0.3909 | ambiguous | 0.332 | benign | -0.022 | Destabilizing | 0.018 | N | 0.388 | neutral | None | None | None | None | N |
| S/E | 0.3795 | ambiguous | 0.3343 | benign | -0.06 | Destabilizing | 0.009 | N | 0.385 | neutral | None | None | None | None | N |
| S/F | 0.1164 | likely_benign | 0.1188 | benign | -1.271 | Destabilizing | None | N | 0.339 | neutral | None | None | None | None | N |
| S/G | 0.1323 | likely_benign | 0.1172 | benign | -1.061 | Destabilizing | None | N | 0.184 | neutral | N | 0.494992536 | None | None | N |
| S/H | 0.2124 | likely_benign | 0.176 | benign | -1.533 | Destabilizing | 0.245 | N | 0.47 | neutral | None | None | None | None | N |
| S/I | 0.0849 | likely_benign | 0.0767 | benign | -0.469 | Destabilizing | 0.002 | N | 0.408 | neutral | N | 0.506281162 | None | None | N |
| S/K | 0.4431 | ambiguous | 0.374 | ambiguous | -0.594 | Destabilizing | None | N | 0.197 | neutral | None | None | None | None | N |
| S/L | 0.0803 | likely_benign | 0.0824 | benign | -0.469 | Destabilizing | 0.004 | N | 0.379 | neutral | None | None | None | None | N |
| S/M | 0.1371 | likely_benign | 0.1259 | benign | -0.083 | Destabilizing | 0.138 | N | 0.472 | neutral | None | None | None | None | N |
| S/N | 0.1176 | likely_benign | 0.0948 | benign | -0.454 | Destabilizing | 0.033 | N | 0.411 | neutral | D | 0.525250924 | None | None | N |
| S/P | 0.9188 | likely_pathogenic | 0.9226 | pathogenic | -0.572 | Destabilizing | 0.085 | N | 0.491 | neutral | None | None | None | None | N |
| S/Q | 0.3152 | likely_benign | 0.2682 | benign | -0.669 | Destabilizing | 0.044 | N | 0.445 | neutral | None | None | None | None | N |
| S/R | 0.3679 | ambiguous | 0.3239 | benign | -0.427 | Destabilizing | 0.017 | N | 0.495 | neutral | N | 0.49392794 | None | None | N |
| S/T | 0.0675 | likely_benign | 0.0635 | benign | -0.549 | Destabilizing | None | N | 0.206 | neutral | N | 0.451502527 | None | None | N |
| S/V | 0.0935 | likely_benign | 0.0889 | benign | -0.572 | Destabilizing | None | N | 0.326 | neutral | None | None | None | None | N |
| S/W | 0.3 | likely_benign | 0.3147 | benign | -1.187 | Destabilizing | 0.788 | D | 0.495 | neutral | None | None | None | None | N |
| S/Y | 0.1431 | likely_benign | 0.1392 | benign | -0.941 | Destabilizing | 0.022 | N | 0.55 | 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.