Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28197 | 84814;84815;84816 | chr2:178561543;178561542;178561541 | chr2:179426270;179426269;179426268 |
| N2AB | 26556 | 79891;79892;79893 | chr2:178561543;178561542;178561541 | chr2:179426270;179426269;179426268 |
| N2A | 25629 | 77110;77111;77112 | chr2:178561543;178561542;178561541 | chr2:179426270;179426269;179426268 |
| N2B | 19132 | 57619;57620;57621 | chr2:178561543;178561542;178561541 | chr2:179426270;179426269;179426268 |
| Novex-1 | 19257 | 57994;57995;57996 | chr2:178561543;178561542;178561541 | chr2:179426270;179426269;179426268 |
| Novex-2 | 19324 | 58195;58196;58197 | chr2:178561543;178561542;178561541 | chr2:179426270;179426269;179426268 |
| 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 | rs769905776  |
0.006 | 0.656 | N | 0.337 | 0.223 | 0.124217242631 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| S/G | rs769905776 |
0.006 | 0.656 | N | 0.337 | 0.223 | 0.124217242631 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| S/G | rs769905776 |
0.006 | 0.656 | N | 0.337 | 0.223 | 0.124217242631 | gnomAD-4.0.0 | 3.7192E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08664E-06 | 0 | 0 |
| S/R | rs781670887 |
-0.043 | 0.942 | N | 0.291 | 0.258 | 0.30212335484 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.24266E-04 | None | 0 | None | 0 | 0 | 0 |
| S/R | rs781670887 |
-0.043 | 0.942 | N | 0.291 | 0.258 | 0.30212335484 | gnomAD-4.0.0 | 2.0534E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 7.57537E-05 | None | 0 | 0 | 0 | 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 | 0.1519 | likely_benign | 0.1449 | benign | -0.2 | Destabilizing | 0.717 | D | 0.395 | neutral | None | None | None | None | I |
| S/C | 0.224 | likely_benign | 0.2348 | benign | -0.355 | Destabilizing | 0.997 | D | 0.418 | neutral | N | 0.499434468 | None | None | I |
| S/D | 0.631 | likely_pathogenic | 0.632 | pathogenic | 0.029 | Stabilizing | 0.754 | D | 0.255 | neutral | None | None | None | None | I |
| S/E | 0.8005 | likely_pathogenic | 0.8164 | pathogenic | -0.081 | Destabilizing | 0.86 | D | 0.255 | neutral | None | None | None | None | I |
| S/F | 0.5354 | ambiguous | 0.5169 | ambiguous | -0.939 | Destabilizing | 0.978 | D | 0.466 | neutral | None | None | None | None | I |
| S/G | 0.1068 | likely_benign | 0.0997 | benign | -0.243 | Destabilizing | 0.656 | D | 0.337 | neutral | N | 0.41285006 | None | None | I |
| S/H | 0.5334 | ambiguous | 0.5631 | ambiguous | -0.6 | Destabilizing | 0.043 | N | 0.301 | neutral | None | None | None | None | I |
| S/I | 0.4595 | ambiguous | 0.4702 | ambiguous | -0.219 | Destabilizing | 0.97 | D | 0.461 | neutral | N | 0.504109569 | None | None | I |
| S/K | 0.8635 | likely_pathogenic | 0.8874 | pathogenic | -0.418 | Destabilizing | 0.86 | D | 0.262 | neutral | None | None | None | None | I |
| S/L | 0.2325 | likely_benign | 0.223 | benign | -0.219 | Destabilizing | 0.86 | D | 0.375 | neutral | None | None | None | None | I |
| S/M | 0.3708 | ambiguous | 0.3598 | ambiguous | -0.122 | Destabilizing | 0.998 | D | 0.359 | neutral | None | None | None | None | I |
| S/N | 0.1507 | likely_benign | 0.1406 | benign | -0.184 | Destabilizing | 0.025 | N | 0.163 | neutral | N | 0.370734078 | None | None | I |
| S/P | 0.5474 | ambiguous | 0.4986 | ambiguous | -0.188 | Destabilizing | 0.993 | D | 0.333 | neutral | None | None | None | None | I |
| S/Q | 0.7066 | likely_pathogenic | 0.7226 | pathogenic | -0.411 | Destabilizing | 0.956 | D | 0.274 | neutral | None | None | None | None | I |
| S/R | 0.813 | likely_pathogenic | 0.8493 | pathogenic | -0.175 | Destabilizing | 0.942 | D | 0.291 | neutral | N | 0.481443353 | None | None | I |
| S/T | 0.1269 | likely_benign | 0.1175 | benign | -0.299 | Destabilizing | 0.822 | D | 0.316 | neutral | N | 0.453064673 | None | None | I |
| S/V | 0.4405 | ambiguous | 0.4403 | ambiguous | -0.188 | Destabilizing | 0.978 | D | 0.417 | neutral | None | None | None | None | I |
| S/W | 0.636 | likely_pathogenic | 0.6516 | pathogenic | -1.018 | Destabilizing | 0.998 | D | 0.644 | neutral | None | None | None | None | I |
| S/Y | 0.3892 | ambiguous | 0.3973 | ambiguous | -0.71 | Destabilizing | 0.915 | D | 0.459 | 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.