Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31764 | 95515;95516;95517 | chr2:178545946;178545945;178545944 | chr2:179410673;179410672;179410671 |
| N2AB | 30123 | 90592;90593;90594 | chr2:178545946;178545945;178545944 | chr2:179410673;179410672;179410671 |
| N2A | 29196 | 87811;87812;87813 | chr2:178545946;178545945;178545944 | chr2:179410673;179410672;179410671 |
| N2B | 22699 | 68320;68321;68322 | chr2:178545946;178545945;178545944 | chr2:179410673;179410672;179410671 |
| Novex-1 | 22824 | 68695;68696;68697 | chr2:178545946;178545945;178545944 | chr2:179410673;179410672;179410671 |
| Novex-2 | 22891 | 68896;68897;68898 | chr2:178545946;178545945;178545944 | chr2:179410673;179410672;179410671 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/N | rs1357116939  |
None | 0.997 | N | 0.497 | 0.361 | 0.370789594751 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.75482E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs1175551497 |
-0.764 | 0.775 | N | 0.273 | 0.18 | 0.158396225186 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs1175551497 |
-0.764 | 0.775 | N | 0.273 | 0.18 | 0.158396225186 | gnomAD-4.0.0 | 1.36838E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.03931E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.067 | likely_benign | 0.0661 | benign | -0.896 | Destabilizing | 0.543 | D | 0.207 | neutral | N | 0.437193931 | None | None | N |
| T/C | 0.3629 | ambiguous | 0.364 | ambiguous | -0.595 | Destabilizing | 1.0 | D | 0.575 | neutral | None | None | None | None | N |
| T/D | 0.332 | likely_benign | 0.3536 | ambiguous | -0.151 | Destabilizing | 0.998 | D | 0.521 | neutral | None | None | None | None | N |
| T/E | 0.2742 | likely_benign | 0.3037 | benign | -0.063 | Destabilizing | 0.998 | D | 0.507 | neutral | None | None | None | None | N |
| T/F | 0.2317 | likely_benign | 0.2302 | benign | -1.05 | Destabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | N |
| T/G | 0.1582 | likely_benign | 0.1625 | benign | -1.173 | Destabilizing | 0.992 | D | 0.439 | neutral | None | None | None | None | N |
| T/H | 0.2282 | likely_benign | 0.2278 | benign | -1.096 | Destabilizing | 1.0 | D | 0.605 | neutral | None | None | None | None | N |
| T/I | 0.1715 | likely_benign | 0.1801 | benign | -0.224 | Destabilizing | 0.998 | D | 0.575 | neutral | N | 0.482452509 | None | None | N |
| T/K | 0.2087 | likely_benign | 0.2258 | benign | -0.323 | Destabilizing | 0.998 | D | 0.523 | neutral | None | None | None | None | N |
| T/L | 0.0999 | likely_benign | 0.1004 | benign | -0.224 | Destabilizing | 0.992 | D | 0.439 | neutral | None | None | None | None | N |
| T/M | 0.0979 | likely_benign | 0.0943 | benign | -0.343 | Destabilizing | 1.0 | D | 0.573 | neutral | None | None | None | None | N |
| T/N | 0.1058 | likely_benign | 0.1049 | benign | -0.634 | Destabilizing | 0.997 | D | 0.497 | neutral | N | 0.511019686 | None | None | N |
| T/P | 0.292 | likely_benign | 0.2848 | benign | -0.419 | Destabilizing | 0.998 | D | 0.585 | neutral | N | 0.509152816 | None | None | N |
| T/Q | 0.193 | likely_benign | 0.1999 | benign | -0.565 | Destabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | N |
| T/R | 0.198 | likely_benign | 0.2099 | benign | -0.213 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | N |
| T/S | 0.0846 | likely_benign | 0.0828 | benign | -0.97 | Destabilizing | 0.775 | D | 0.273 | neutral | N | 0.4435439 | None | None | N |
| T/V | 0.1148 | likely_benign | 0.1195 | benign | -0.419 | Destabilizing | 0.992 | D | 0.371 | neutral | None | None | None | None | N |
| T/W | 0.6273 | likely_pathogenic | 0.6576 | pathogenic | -1.103 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | N |
| T/Y | 0.2654 | likely_benign | 0.2642 | benign | -0.766 | Destabilizing | 1.0 | D | 0.621 | 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.