Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14915 | 44968;44969;44970 | chr2:178624537;178624536;178624535 | chr2:179489264;179489263;179489262 |
| N2AB | 13274 | 40045;40046;40047 | chr2:178624537;178624536;178624535 | chr2:179489264;179489263;179489262 |
| N2A | 12347 | 37264;37265;37266 | chr2:178624537;178624536;178624535 | chr2:179489264;179489263;179489262 |
| N2B | 5850 | 17773;17774;17775 | chr2:178624537;178624536;178624535 | chr2:179489264;179489263;179489262 |
| Novex-1 | 5975 | 18148;18149;18150 | chr2:178624537;178624536;178624535 | chr2:179489264;179489263;179489262 |
| Novex-2 | 6042 | 18349;18350;18351 | chr2:178624537;178624536;178624535 | chr2:179489264;179489263;179489262 |
| 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/A | rs878854310  |
None | 0.201 | N | 0.385 | 0.128 | 0.177238962908 | gnomAD-4.0.0 | 2.73844E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.83112E-05 | 0 | None | 0 | 0 | 2.6996E-06 | 0 | 0 |
| T/I | rs765495409 |
-0.084 | 0.681 | N | 0.345 | 0.321 | 0.416454006429 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.14E-05 | 0 |
| T/I | rs765495409 |
-0.084 | 0.681 | N | 0.345 | 0.321 | 0.416454006429 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| T/I | rs765495409 |
-0.084 | 0.681 | N | 0.345 | 0.321 | 0.416454006429 | gnomAD-4.0.0 | 5.58112E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.78432E-06 | 0 | 1.60287E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1296 | likely_benign | 0.1037 | benign | -0.703 | Destabilizing | 0.201 | N | 0.385 | neutral | N | 0.506468355 | None | None | N |
| T/C | 0.5907 | likely_pathogenic | 0.5769 | pathogenic | -0.491 | Destabilizing | 0.992 | D | 0.375 | neutral | None | None | None | None | N |
| T/D | 0.4215 | ambiguous | 0.3794 | ambiguous | -1.12 | Destabilizing | 0.85 | D | 0.351 | neutral | None | None | None | None | N |
| T/E | 0.3642 | ambiguous | 0.3112 | benign | -1.115 | Destabilizing | 0.447 | N | 0.371 | neutral | None | None | None | None | N |
| T/F | 0.3353 | likely_benign | 0.2587 | benign | -0.818 | Destabilizing | 0.739 | D | 0.436 | neutral | None | None | None | None | N |
| T/G | 0.2446 | likely_benign | 0.2194 | benign | -0.969 | Destabilizing | 0.617 | D | 0.429 | neutral | None | None | None | None | N |
| T/H | 0.3159 | likely_benign | 0.2528 | benign | -1.362 | Destabilizing | 0.85 | D | 0.431 | neutral | None | None | None | None | N |
| T/I | 0.2683 | likely_benign | 0.2272 | benign | -0.082 | Destabilizing | 0.681 | D | 0.345 | neutral | N | 0.512123715 | None | None | N |
| T/K | 0.1477 | likely_benign | 0.1312 | benign | -0.922 | Destabilizing | 0.005 | N | 0.268 | neutral | None | None | None | None | N |
| T/L | 0.1138 | likely_benign | 0.0856 | benign | -0.082 | Destabilizing | 0.25 | N | 0.385 | neutral | None | None | None | None | N |
| T/M | 0.1401 | likely_benign | 0.1015 | benign | 0.368 | Stabilizing | 0.25 | N | 0.387 | neutral | None | None | None | None | N |
| T/N | 0.1428 | likely_benign | 0.1247 | benign | -1.001 | Destabilizing | 0.549 | D | 0.386 | neutral | N | 0.511388823 | None | None | N |
| T/P | 0.3765 | ambiguous | 0.3561 | ambiguous | -0.257 | Destabilizing | 0.896 | D | 0.349 | neutral | D | 0.648644152 | None | None | N |
| T/Q | 0.2384 | likely_benign | 0.1906 | benign | -1.214 | Destabilizing | 0.739 | D | 0.351 | neutral | None | None | None | None | N |
| T/R | 0.1666 | likely_benign | 0.1327 | benign | -0.629 | Destabilizing | 0.739 | D | 0.323 | neutral | None | None | None | None | N |
| T/S | 0.1161 | likely_benign | 0.1019 | benign | -1.116 | Destabilizing | 0.045 | N | 0.305 | neutral | N | 0.43497502 | None | None | N |
| T/V | 0.2272 | likely_benign | 0.1978 | benign | -0.257 | Destabilizing | 0.447 | N | 0.379 | neutral | None | None | None | None | N |
| T/W | 0.7899 | likely_pathogenic | 0.7302 | pathogenic | -0.83 | Destabilizing | 0.977 | D | 0.464 | neutral | None | None | None | None | N |
| T/Y | 0.4353 | ambiguous | 0.3646 | ambiguous | -0.563 | Destabilizing | 0.012 | N | 0.338 | 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.