Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23711 | 71356;71357;71358 | chr2:178575001;178575000;178574999 | chr2:179439728;179439727;179439726 |
| N2AB | 22070 | 66433;66434;66435 | chr2:178575001;178575000;178574999 | chr2:179439728;179439727;179439726 |
| N2A | 21143 | 63652;63653;63654 | chr2:178575001;178575000;178574999 | chr2:179439728;179439727;179439726 |
| N2B | 14646 | 44161;44162;44163 | chr2:178575001;178575000;178574999 | chr2:179439728;179439727;179439726 |
| Novex-1 | 14771 | 44536;44537;44538 | chr2:178575001;178575000;178574999 | chr2:179439728;179439727;179439726 |
| Novex-2 | 14838 | 44737;44738;44739 | chr2:178575001;178575000;178574999 | chr2:179439728;179439727;179439726 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs1311167365  |
-0.556 | 0.005 | N | 0.327 | 0.102 | 0.239901079897 | 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 |
| I/M | rs1311167365 |
-0.556 | 0.005 | N | 0.327 | 0.102 | 0.239901079897 | gnomAD-4.0.0 | 3.42189E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49792E-06 | 0 | 0 |
| I/T | rs752317656 |
-0.331 | None | N | 0.183 | 0.09 | 0.511275995344 | gnomAD-2.1.1 | 5.64E-05 | None | None | None | None | I | None | 0 | 1.16144E-04 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 5.34E-05 | 1.66223E-04 |
| I/T | rs752317656 |
-0.331 | None | N | 0.183 | 0.09 | 0.511275995344 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs752317656 |
-0.331 | None | N | 0.183 | 0.09 | 0.511275995344 | gnomAD-4.0.0 | 2.10764E-05 | None | None | None | None | I | None | 0 | 1.00087E-04 | None | 0 | 2.23784E-05 | None | 0 | 0 | 1.78028E-05 | 6.58906E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1126 | likely_benign | 0.1115 | benign | -0.506 | Destabilizing | 0.016 | N | 0.409 | neutral | None | None | None | None | I |
| I/C | 0.5478 | ambiguous | 0.5374 | ambiguous | -0.831 | Destabilizing | 0.356 | N | 0.355 | neutral | None | None | None | None | I |
| I/D | 0.4871 | ambiguous | 0.4147 | ambiguous | -0.234 | Destabilizing | 0.072 | N | 0.355 | neutral | None | None | None | None | I |
| I/E | 0.427 | ambiguous | 0.375 | ambiguous | -0.323 | Destabilizing | 0.072 | N | 0.369 | neutral | None | None | None | None | I |
| I/F | 0.1819 | likely_benign | 0.1568 | benign | -0.631 | Destabilizing | 0.055 | N | 0.324 | neutral | D | 0.530229883 | None | None | I |
| I/G | 0.3824 | ambiguous | 0.3581 | ambiguous | -0.613 | Destabilizing | 0.072 | N | 0.382 | neutral | None | None | None | None | I |
| I/H | 0.3672 | ambiguous | 0.3411 | ambiguous | 0.066 | Stabilizing | 0.864 | D | 0.335 | neutral | None | None | None | None | I |
| I/K | 0.2687 | likely_benign | 0.2466 | benign | -0.37 | Destabilizing | 0.072 | N | 0.388 | neutral | None | None | None | None | I |
| I/L | 0.0946 | likely_benign | 0.0943 | benign | -0.342 | Destabilizing | None | N | 0.147 | neutral | N | 0.489940698 | None | None | I |
| I/M | 0.081 | likely_benign | 0.0861 | benign | -0.608 | Destabilizing | 0.005 | N | 0.327 | neutral | N | 0.475107319 | None | None | I |
| I/N | 0.1545 | likely_benign | 0.1599 | benign | -0.264 | Destabilizing | 0.055 | N | 0.365 | neutral | N | 0.48976734 | None | None | I |
| I/P | 0.3738 | ambiguous | 0.3401 | ambiguous | -0.369 | Destabilizing | 0.356 | N | 0.372 | neutral | None | None | None | None | I |
| I/Q | 0.3046 | likely_benign | 0.2979 | benign | -0.438 | Destabilizing | 0.356 | N | 0.374 | neutral | None | None | None | None | I |
| I/R | 0.2233 | likely_benign | 0.1907 | benign | 0.113 | Stabilizing | 0.214 | N | 0.375 | neutral | None | None | None | None | I |
| I/S | 0.1263 | likely_benign | 0.1315 | benign | -0.658 | Destabilizing | 0.002 | N | 0.251 | neutral | N | 0.440605169 | None | None | I |
| I/T | 0.0798 | likely_benign | 0.0844 | benign | -0.644 | Destabilizing | None | N | 0.183 | neutral | N | 0.480974498 | None | None | I |
| I/V | 0.0702 | likely_benign | 0.0635 | benign | -0.369 | Destabilizing | 0.005 | N | 0.335 | neutral | N | 0.471701654 | None | None | I |
| I/W | 0.7692 | likely_pathogenic | 0.7116 | pathogenic | -0.647 | Destabilizing | 0.864 | D | 0.349 | neutral | None | None | None | None | I |
| I/Y | 0.4693 | ambiguous | 0.443 | ambiguous | -0.416 | Destabilizing | 0.356 | N | 0.36 | 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.