Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15372 | 46339;46340;46341 | chr2:178620407;178620406;178620405 | chr2:179485134;179485133;179485132 |
| N2AB | 13731 | 41416;41417;41418 | chr2:178620407;178620406;178620405 | chr2:179485134;179485133;179485132 |
| N2A | 12804 | 38635;38636;38637 | chr2:178620407;178620406;178620405 | chr2:179485134;179485133;179485132 |
| N2B | 6307 | 19144;19145;19146 | chr2:178620407;178620406;178620405 | chr2:179485134;179485133;179485132 |
| Novex-1 | 6432 | 19519;19520;19521 | chr2:178620407;178620406;178620405 | chr2:179485134;179485133;179485132 |
| Novex-2 | 6499 | 19720;19721;19722 | chr2:178620407;178620406;178620405 | chr2:179485134;179485133;179485132 |
| 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/L | None | None | 0.005 | N | 0.427 | 0.043 | 0.290590437066 | gnomAD-4.0.0 | 6.8481E-07 | None | None | None | None | N | None | 0 | 0 | None | 3.83759E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | None | None | None | N | 0.329 | 0.162 | 0.376745185316 | gnomAD-4.0.0 | 1.59452E-06 | None | None | None | None | N | None | 0 | 2.29074E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs2154211008  |
None | None | N | 0.171 | 0.04 | 0.225215365344 | gnomAD-4.0.0 | 6.8481E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00077E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1564 | likely_benign | 0.1731 | benign | -2.337 | Highly Destabilizing | 0.007 | N | 0.484 | neutral | None | None | None | None | N |
| I/C | 0.4939 | ambiguous | 0.5443 | ambiguous | -1.814 | Destabilizing | 0.356 | N | 0.591 | neutral | None | None | None | None | N |
| I/D | 0.5892 | likely_pathogenic | 0.614 | pathogenic | -2.19 | Highly Destabilizing | 0.072 | N | 0.59 | neutral | None | None | None | None | N |
| I/E | 0.3457 | ambiguous | 0.3795 | ambiguous | -2.032 | Highly Destabilizing | 0.072 | N | 0.605 | neutral | None | None | None | None | N |
| I/F | 0.1691 | likely_benign | 0.1815 | benign | -1.411 | Destabilizing | 0.055 | N | 0.59 | neutral | N | 0.449764175 | None | None | N |
| I/G | 0.5337 | ambiguous | 0.5631 | ambiguous | -2.811 | Highly Destabilizing | 0.072 | N | 0.597 | neutral | None | None | None | None | N |
| I/H | 0.3428 | ambiguous | 0.351 | ambiguous | -2.084 | Highly Destabilizing | 0.628 | D | 0.615 | neutral | None | None | None | None | N |
| I/K | 0.2979 | likely_benign | 0.2841 | benign | -1.62 | Destabilizing | 0.072 | N | 0.605 | neutral | None | None | None | None | N |
| I/L | 0.1382 | likely_benign | 0.1412 | benign | -1.006 | Destabilizing | 0.005 | N | 0.427 | neutral | N | 0.443689053 | None | None | N |
| I/M | 0.092 | likely_benign | 0.0958 | benign | -1.086 | Destabilizing | 0.171 | N | 0.565 | neutral | N | 0.435271937 | None | None | N |
| I/N | 0.2242 | likely_benign | 0.1911 | benign | -1.768 | Destabilizing | 0.055 | N | 0.587 | neutral | N | 0.45197386 | None | None | N |
| I/P | 0.9616 | likely_pathogenic | 0.9671 | pathogenic | -1.427 | Destabilizing | 0.136 | N | 0.616 | neutral | None | None | None | None | N |
| I/Q | 0.2894 | likely_benign | 0.2908 | benign | -1.75 | Destabilizing | 0.356 | N | 0.619 | neutral | None | None | None | None | N |
| I/R | 0.2119 | likely_benign | 0.2024 | benign | -1.255 | Destabilizing | 0.214 | N | 0.627 | neutral | None | None | None | None | N |
| I/S | 0.1445 | likely_benign | 0.1349 | benign | -2.52 | Highly Destabilizing | 0.012 | N | 0.561 | neutral | N | 0.351246926 | None | None | N |
| I/T | 0.0629 | likely_benign | 0.0663 | benign | -2.226 | Highly Destabilizing | None | N | 0.329 | neutral | N | 0.297747162 | None | None | N |
| I/V | 0.0729 | likely_benign | 0.0767 | benign | -1.427 | Destabilizing | None | N | 0.171 | neutral | N | 0.414231823 | None | None | N |
| I/W | 0.6789 | likely_pathogenic | 0.7601 | pathogenic | -1.636 | Destabilizing | 0.864 | D | 0.641 | neutral | None | None | None | None | N |
| I/Y | 0.395 | ambiguous | 0.42 | ambiguous | -1.38 | Destabilizing | 0.356 | N | 0.607 | 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.