Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15517 | 46774;46775;46776 | chr2:178619768;178619767;178619766 | chr2:179484495;179484494;179484493 |
| N2AB | 13876 | 41851;41852;41853 | chr2:178619768;178619767;178619766 | chr2:179484495;179484494;179484493 |
| N2A | 12949 | 39070;39071;39072 | chr2:178619768;178619767;178619766 | chr2:179484495;179484494;179484493 |
| N2B | 6452 | 19579;19580;19581 | chr2:178619768;178619767;178619766 | chr2:179484495;179484494;179484493 |
| Novex-1 | 6577 | 19954;19955;19956 | chr2:178619768;178619767;178619766 | chr2:179484495;179484494;179484493 |
| Novex-2 | 6644 | 20155;20156;20157 | chr2:178619768;178619767;178619766 | chr2:179484495;179484494;179484493 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs1349699547  |
0.44 | 0.801 | N | 0.377 | 0.418 | 0.763603987931 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| M/T | rs1349699547 |
0.44 | 0.801 | N | 0.377 | 0.418 | 0.763603987931 | gnomAD-4.0.0 | 1.36942E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80012E-06 | 0 | 0 |
| M/V | rs751464964 |
0.138 | 0.267 | N | 0.285 | 0.273 | 0.593685261966 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.30753E-04 | None | 0 | 0 | 0 |
| M/V | rs751464964 |
0.138 | 0.267 | N | 0.285 | 0.273 | 0.593685261966 | gnomAD-4.0.0 | 9.56376E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.60215E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.629 | likely_pathogenic | 0.5512 | ambiguous | -0.636 | Destabilizing | 0.688 | D | 0.404 | neutral | None | None | None | None | I |
| M/C | 0.8308 | likely_pathogenic | 0.8359 | pathogenic | -0.584 | Destabilizing | 0.998 | D | 0.379 | neutral | None | None | None | None | I |
| M/D | 0.9242 | likely_pathogenic | 0.9032 | pathogenic | 0.193 | Stabilizing | 0.991 | D | 0.401 | neutral | None | None | None | None | I |
| M/E | 0.7155 | likely_pathogenic | 0.6702 | pathogenic | 0.151 | Stabilizing | 0.991 | D | 0.365 | neutral | None | None | None | None | I |
| M/F | 0.543 | ambiguous | 0.5535 | ambiguous | -0.177 | Destabilizing | 0.842 | D | 0.387 | neutral | None | None | None | None | I |
| M/G | 0.8566 | likely_pathogenic | 0.8307 | pathogenic | -0.831 | Destabilizing | 0.991 | D | 0.395 | neutral | None | None | None | None | I |
| M/H | 0.6319 | likely_pathogenic | 0.5952 | pathogenic | 0.031 | Stabilizing | 0.998 | D | 0.389 | neutral | None | None | None | None | I |
| M/I | 0.6542 | likely_pathogenic | 0.5657 | pathogenic | -0.21 | Destabilizing | 0.012 | N | 0.218 | neutral | N | 0.46947419 | None | None | I |
| M/K | 0.3727 | ambiguous | 0.3538 | ambiguous | 0.212 | Stabilizing | 0.891 | D | 0.391 | neutral | N | 0.437466282 | None | None | I |
| M/L | 0.2458 | likely_benign | 0.244 | benign | -0.21 | Destabilizing | 0.136 | N | 0.259 | neutral | N | 0.477023038 | None | None | I |
| M/N | 0.7 | likely_pathogenic | 0.6758 | pathogenic | 0.344 | Stabilizing | 0.991 | D | 0.399 | neutral | None | None | None | None | I |
| M/P | 0.9919 | likely_pathogenic | 0.9897 | pathogenic | -0.323 | Destabilizing | 0.991 | D | 0.4 | neutral | None | None | None | None | I |
| M/Q | 0.3447 | ambiguous | 0.3147 | benign | 0.191 | Stabilizing | 0.991 | D | 0.382 | neutral | None | None | None | None | I |
| M/R | 0.3594 | ambiguous | 0.3462 | ambiguous | 0.735 | Stabilizing | 0.989 | D | 0.381 | neutral | N | 0.45524425 | None | None | I |
| M/S | 0.6876 | likely_pathogenic | 0.6196 | pathogenic | -0.131 | Destabilizing | 0.915 | D | 0.385 | neutral | None | None | None | None | I |
| M/T | 0.4723 | ambiguous | 0.3543 | ambiguous | -0.071 | Destabilizing | 0.801 | D | 0.377 | neutral | N | 0.426609179 | None | None | I |
| M/V | 0.1911 | likely_benign | 0.1466 | benign | -0.323 | Destabilizing | 0.267 | N | 0.285 | neutral | N | 0.44200905 | None | None | I |
| M/W | 0.8459 | likely_pathogenic | 0.8401 | pathogenic | -0.148 | Destabilizing | 0.998 | D | 0.408 | neutral | None | None | None | None | I |
| M/Y | 0.7382 | likely_pathogenic | 0.7319 | pathogenic | -0.034 | Destabilizing | 0.991 | D | 0.379 | 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.