Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27993 | 84202;84203;84204 | chr2:178562155;178562154;178562153 | chr2:179426882;179426881;179426880 |
| N2AB | 26352 | 79279;79280;79281 | chr2:178562155;178562154;178562153 | chr2:179426882;179426881;179426880 |
| N2A | 25425 | 76498;76499;76500 | chr2:178562155;178562154;178562153 | chr2:179426882;179426881;179426880 |
| N2B | 18928 | 57007;57008;57009 | chr2:178562155;178562154;178562153 | chr2:179426882;179426881;179426880 |
| Novex-1 | 19053 | 57382;57383;57384 | chr2:178562155;178562154;178562153 | chr2:179426882;179426881;179426880 |
| Novex-2 | 19120 | 57583;57584;57585 | chr2:178562155;178562154;178562153 | chr2:179426882;179426881;179426880 |
| 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 | rs752491962  |
-0.51 | None | N | 0.106 | 0.081 | 0.241664281697 | gnomAD-2.1.1 | 7.18E-06 | None | None | None | None | I | None | 4.15E-05 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| T/A | rs752491962 |
-0.51 | None | N | 0.106 | 0.081 | 0.241664281697 | gnomAD-4.0.0 | 4.77852E-06 | None | None | None | None | I | None | 5.66059E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86008E-06 | 1.43382E-05 | 0 |
| T/I | rs377614000 |
None | 0.213 | N | 0.377 | 0.278 | 0.50143340055 | gnomAD-4.0.0 | 6.84518E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65744E-05 |
| T/N | rs377614000 |
-0.057 | 0.213 | N | 0.24 | 0.243 | None | gnomAD-2.1.1 | 2.16E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.73E-05 | 0 |
| T/N | rs377614000 |
-0.057 | 0.213 | N | 0.24 | 0.243 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17606E-04 | 0 | 0 |
| T/N | rs377614000 |
-0.057 | 0.213 | N | 0.24 | 0.243 | None | gnomAD-4.0.0 | 4.40168E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.68012E-05 | 0 | 6.40759E-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 | 0.0647 | likely_benign | 0.0674 | benign | -0.385 | Destabilizing | None | N | 0.106 | neutral | N | 0.490172772 | None | None | I |
| T/C | 0.2944 | likely_benign | 0.2915 | benign | -0.307 | Destabilizing | 0.836 | D | 0.456 | neutral | None | None | None | None | I |
| T/D | 0.298 | likely_benign | 0.3006 | benign | 0.185 | Stabilizing | 0.129 | N | 0.346 | neutral | None | None | None | None | I |
| T/E | 0.2295 | likely_benign | 0.2313 | benign | 0.122 | Stabilizing | 0.004 | N | 0.179 | neutral | None | None | None | None | I |
| T/F | 0.1778 | likely_benign | 0.1788 | benign | -0.851 | Destabilizing | 0.836 | D | 0.523 | neutral | None | None | None | None | I |
| T/G | 0.1958 | likely_benign | 0.2002 | benign | -0.532 | Destabilizing | 0.129 | N | 0.313 | neutral | None | None | None | None | I |
| T/H | 0.1979 | likely_benign | 0.1978 | benign | -0.804 | Destabilizing | 0.836 | D | 0.471 | neutral | None | None | None | None | I |
| T/I | 0.0967 | likely_benign | 0.0917 | benign | -0.117 | Destabilizing | 0.213 | N | 0.377 | neutral | N | 0.487556115 | None | None | I |
| T/K | 0.1499 | likely_benign | 0.1474 | benign | -0.371 | Destabilizing | 0.129 | N | 0.348 | neutral | None | None | None | None | I |
| T/L | 0.0852 | likely_benign | 0.0815 | benign | -0.117 | Destabilizing | 0.129 | N | 0.324 | neutral | None | None | None | None | I |
| T/M | 0.0853 | likely_benign | 0.0851 | benign | -0.003 | Destabilizing | 0.836 | D | 0.458 | neutral | None | None | None | None | I |
| T/N | 0.1075 | likely_benign | 0.1053 | benign | -0.2 | Destabilizing | 0.213 | N | 0.24 | neutral | N | 0.4841623 | None | None | I |
| T/P | 0.2614 | likely_benign | 0.3154 | benign | -0.177 | Destabilizing | 0.523 | D | 0.409 | neutral | N | 0.506002765 | None | None | I |
| T/Q | 0.1796 | likely_benign | 0.183 | benign | -0.393 | Destabilizing | 0.418 | N | 0.413 | neutral | None | None | None | None | I |
| T/R | 0.1368 | likely_benign | 0.1432 | benign | -0.111 | Destabilizing | 0.418 | N | 0.436 | neutral | None | None | None | None | I |
| T/S | 0.0892 | likely_benign | 0.0892 | benign | -0.416 | Destabilizing | 0.003 | N | 0.161 | neutral | N | 0.503907286 | None | None | I |
| T/V | 0.0809 | likely_benign | 0.0765 | benign | -0.177 | Destabilizing | 0.004 | N | 0.141 | neutral | None | None | None | None | I |
| T/W | 0.5137 | ambiguous | 0.5426 | ambiguous | -0.862 | Destabilizing | 0.983 | D | 0.495 | neutral | None | None | None | None | I |
| T/Y | 0.2329 | likely_benign | 0.2411 | benign | -0.571 | Destabilizing | 0.94 | D | 0.491 | 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.