Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19449 | 58570;58571;58572 | chr2:178594048;178594047;178594046 | chr2:179458775;179458774;179458773 |
| N2AB | 17808 | 53647;53648;53649 | chr2:178594048;178594047;178594046 | chr2:179458775;179458774;179458773 |
| N2A | 16881 | 50866;50867;50868 | chr2:178594048;178594047;178594046 | chr2:179458775;179458774;179458773 |
| N2B | 10384 | 31375;31376;31377 | chr2:178594048;178594047;178594046 | chr2:179458775;179458774;179458773 |
| Novex-1 | 10509 | 31750;31751;31752 | chr2:178594048;178594047;178594046 | chr2:179458775;179458774;179458773 |
| Novex-2 | 10576 | 31951;31952;31953 | chr2:178594048;178594047;178594046 | chr2:179458775;179458774;179458773 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs1179903616  |
-1.208 | 0.324 | D | 0.487 | 0.464 | 0.647137792213 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| A/D | rs1179903616 |
-1.208 | 0.324 | D | 0.487 | 0.464 | 0.647137792213 | gnomAD-4.0.0 | 1.59179E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77886E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/P | None | None | 0.773 | N | 0.551 | 0.52 | 0.346085882481 | gnomAD-4.0.0 | 6.84305E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99551E-07 | 0 | 0 |
| A/S | rs753417375 |
-1.197 | 0.001 | N | 0.175 | 0.139 | 0.16115917748 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| A/S | rs753417375 |
-1.197 | 0.001 | N | 0.175 | 0.139 | 0.16115917748 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/S | rs753417375 |
-1.197 | 0.001 | N | 0.175 | 0.139 | 0.16115917748 | gnomAD-4.0.0 | 5.5783E-06 | None | None | None | None | N | None | 0 | 1.66806E-05 | None | 0 | 0 | None | 0 | 0 | 6.78164E-06 | 0 | 0 |
| A/V | None | None | 0.193 | N | 0.449 | 0.178 | 0.357724736475 | gnomAD-4.0.0 | 1.59179E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85912E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5628 | ambiguous | 0.5397 | ambiguous | -1.565 | Destabilizing | 0.944 | D | 0.517 | neutral | None | None | None | None | N |
| A/D | 0.9637 | likely_pathogenic | 0.9504 | pathogenic | -2.541 | Highly Destabilizing | 0.324 | N | 0.487 | neutral | D | 0.53700117 | None | None | N |
| A/E | 0.9506 | likely_pathogenic | 0.927 | pathogenic | -2.403 | Highly Destabilizing | 0.241 | N | 0.519 | neutral | None | None | None | None | N |
| A/F | 0.9381 | likely_pathogenic | 0.9185 | pathogenic | -0.994 | Destabilizing | 0.818 | D | 0.547 | neutral | None | None | None | None | N |
| A/G | 0.2228 | likely_benign | 0.222 | benign | -1.812 | Destabilizing | 0.001 | N | 0.191 | neutral | N | 0.504653774 | None | None | N |
| A/H | 0.9794 | likely_pathogenic | 0.9717 | pathogenic | -1.953 | Destabilizing | 0.944 | D | 0.537 | neutral | None | None | None | None | N |
| A/I | 0.7043 | likely_pathogenic | 0.6265 | pathogenic | -0.353 | Destabilizing | 0.69 | D | 0.553 | neutral | None | None | None | None | N |
| A/K | 0.9913 | likely_pathogenic | 0.9851 | pathogenic | -1.502 | Destabilizing | 0.241 | N | 0.52 | neutral | None | None | None | None | N |
| A/L | 0.6786 | likely_pathogenic | 0.6033 | pathogenic | -0.353 | Destabilizing | 0.241 | N | 0.457 | neutral | None | None | None | None | N |
| A/M | 0.747 | likely_pathogenic | 0.6797 | pathogenic | -0.61 | Destabilizing | 0.981 | D | 0.538 | neutral | None | None | None | None | N |
| A/N | 0.89 | likely_pathogenic | 0.862 | pathogenic | -1.687 | Destabilizing | 0.527 | D | 0.497 | neutral | None | None | None | None | N |
| A/P | 0.7192 | likely_pathogenic | 0.6775 | pathogenic | -0.664 | Destabilizing | 0.773 | D | 0.551 | neutral | N | 0.50276767 | None | None | N |
| A/Q | 0.9548 | likely_pathogenic | 0.9352 | pathogenic | -1.625 | Destabilizing | 0.69 | D | 0.553 | neutral | None | None | None | None | N |
| A/R | 0.9811 | likely_pathogenic | 0.9702 | pathogenic | -1.379 | Destabilizing | 0.69 | D | 0.546 | neutral | None | None | None | None | N |
| A/S | 0.1346 | likely_benign | 0.1371 | benign | -2.093 | Highly Destabilizing | 0.001 | N | 0.175 | neutral | N | 0.51139898 | None | None | N |
| A/T | 0.2034 | likely_benign | 0.1633 | benign | -1.847 | Destabilizing | 0.006 | N | 0.288 | neutral | D | 0.528099229 | None | None | N |
| A/V | 0.3372 | likely_benign | 0.2752 | benign | -0.664 | Destabilizing | 0.193 | N | 0.449 | neutral | N | 0.492516857 | None | None | N |
| A/W | 0.9897 | likely_pathogenic | 0.9843 | pathogenic | -1.593 | Destabilizing | 0.981 | D | 0.589 | neutral | None | None | None | None | N |
| A/Y | 0.9701 | likely_pathogenic | 0.9596 | pathogenic | -1.143 | Destabilizing | 0.932 | D | 0.557 | 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.