Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28198 | 84817;84818;84819 | chr2:178561540;178561539;178561538 | chr2:179426267;179426266;179426265 |
| N2AB | 26557 | 79894;79895;79896 | chr2:178561540;178561539;178561538 | chr2:179426267;179426266;179426265 |
| N2A | 25630 | 77113;77114;77115 | chr2:178561540;178561539;178561538 | chr2:179426267;179426266;179426265 |
| N2B | 19133 | 57622;57623;57624 | chr2:178561540;178561539;178561538 | chr2:179426267;179426266;179426265 |
| Novex-1 | 19258 | 57997;57998;57999 | chr2:178561540;178561539;178561538 | chr2:179426267;179426266;179426265 |
| Novex-2 | 19325 | 58198;58199;58200 | chr2:178561540;178561539;178561538 | chr2:179426267;179426266;179426265 |
| 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/N | None | None | 0.983 | N | 0.503 | 0.281 | 0.199424873507 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/T | rs886039057  |
None | 0.892 | D | 0.401 | 0.22 | 0.166414681773 | gnomAD-4.0.0 | 1.20032E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1659 | likely_benign | 0.1542 | benign | -0.551 | Destabilizing | 0.033 | N | 0.262 | neutral | None | None | None | None | N |
| S/C | 0.261 | likely_benign | 0.2252 | benign | -0.366 | Destabilizing | 0.995 | D | 0.559 | neutral | N | 0.519858653 | None | None | N |
| S/D | 0.9191 | likely_pathogenic | 0.9044 | pathogenic | 0.317 | Stabilizing | 0.957 | D | 0.466 | neutral | None | None | None | None | N |
| S/E | 0.9549 | likely_pathogenic | 0.9524 | pathogenic | 0.252 | Stabilizing | 0.916 | D | 0.435 | neutral | None | None | None | None | N |
| S/F | 0.8267 | likely_pathogenic | 0.8124 | pathogenic | -0.99 | Destabilizing | 0.987 | D | 0.553 | neutral | None | None | None | None | N |
| S/G | 0.1361 | likely_benign | 0.1231 | benign | -0.711 | Destabilizing | 0.805 | D | 0.41 | neutral | N | 0.469972752 | None | None | N |
| S/H | 0.8439 | likely_pathogenic | 0.8193 | pathogenic | -1.176 | Destabilizing | 0.999 | D | 0.557 | neutral | None | None | None | None | N |
| S/I | 0.8609 | likely_pathogenic | 0.8388 | pathogenic | -0.253 | Destabilizing | 0.967 | D | 0.53 | neutral | N | 0.508248858 | None | None | N |
| S/K | 0.9765 | likely_pathogenic | 0.9734 | pathogenic | -0.563 | Destabilizing | 0.916 | D | 0.435 | neutral | None | None | None | None | N |
| S/L | 0.4087 | ambiguous | 0.368 | ambiguous | -0.253 | Destabilizing | 0.845 | D | 0.439 | neutral | None | None | None | None | N |
| S/M | 0.6326 | likely_pathogenic | 0.595 | pathogenic | -0.02 | Destabilizing | 0.999 | D | 0.557 | neutral | None | None | None | None | N |
| S/N | 0.5438 | ambiguous | 0.4417 | ambiguous | -0.335 | Destabilizing | 0.983 | D | 0.503 | neutral | N | 0.490065243 | None | None | N |
| S/P | 0.9683 | likely_pathogenic | 0.9704 | pathogenic | -0.321 | Destabilizing | 0.987 | D | 0.522 | neutral | None | None | None | None | N |
| S/Q | 0.892 | likely_pathogenic | 0.8814 | pathogenic | -0.528 | Destabilizing | 0.987 | D | 0.523 | neutral | None | None | None | None | N |
| S/R | 0.957 | likely_pathogenic | 0.9536 | pathogenic | -0.404 | Destabilizing | 0.983 | D | 0.518 | neutral | N | 0.49158618 | None | None | N |
| S/T | 0.2442 | likely_benign | 0.2176 | benign | -0.46 | Destabilizing | 0.892 | D | 0.401 | neutral | D | 0.522327184 | None | None | N |
| S/V | 0.7333 | likely_pathogenic | 0.6975 | pathogenic | -0.321 | Destabilizing | 0.95 | D | 0.495 | neutral | None | None | None | None | N |
| S/W | 0.8979 | likely_pathogenic | 0.8931 | pathogenic | -0.967 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| S/Y | 0.776 | likely_pathogenic | 0.7482 | pathogenic | -0.709 | Destabilizing | 0.996 | D | 0.564 | 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.