Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23357 | 70294;70295;70296 | chr2:178576063;178576062;178576061 | chr2:179440790;179440789;179440788 |
| N2AB | 21716 | 65371;65372;65373 | chr2:178576063;178576062;178576061 | chr2:179440790;179440789;179440788 |
| N2A | 20789 | 62590;62591;62592 | chr2:178576063;178576062;178576061 | chr2:179440790;179440789;179440788 |
| N2B | 14292 | 43099;43100;43101 | chr2:178576063;178576062;178576061 | chr2:179440790;179440789;179440788 |
| Novex-1 | 14417 | 43474;43475;43476 | chr2:178576063;178576062;178576061 | chr2:179440790;179440789;179440788 |
| Novex-2 | 14484 | 43675;43676;43677 | chr2:178576063;178576062;178576061 | chr2:179440790;179440789;179440788 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs375401995  |
-0.084 | 0.006 | N | 0.335 | 0.147 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65837E-04 |
| R/T | rs375401995 |
-0.133 | 0.822 | D | 0.581 | 0.408 | 0.496891249646 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 1.65837E-04 |
| R/T | rs375401995 |
-0.133 | 0.822 | D | 0.581 | 0.408 | 0.496891249646 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/T | rs375401995 |
-0.133 | 0.822 | D | 0.581 | 0.408 | 0.496891249646 | gnomAD-4.0.0 | 8.05747E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01727E-05 | 0 | 1.60149E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9373 | likely_pathogenic | 0.9274 | pathogenic | 0.052 | Stabilizing | 0.754 | D | 0.609 | neutral | None | None | None | None | I |
| R/C | 0.723 | likely_pathogenic | 0.6637 | pathogenic | -0.332 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | I |
| R/D | 0.9777 | likely_pathogenic | 0.9757 | pathogenic | -0.203 | Destabilizing | 0.956 | D | 0.621 | neutral | None | None | None | None | I |
| R/E | 0.8767 | likely_pathogenic | 0.8529 | pathogenic | -0.124 | Destabilizing | 0.754 | D | 0.595 | neutral | None | None | None | None | I |
| R/F | 0.9556 | likely_pathogenic | 0.9507 | pathogenic | -0.169 | Destabilizing | 0.993 | D | 0.675 | neutral | None | None | None | None | I |
| R/G | 0.9067 | likely_pathogenic | 0.8976 | pathogenic | -0.142 | Destabilizing | 0.822 | D | 0.604 | neutral | N | 0.521687484 | None | None | I |
| R/H | 0.3685 | ambiguous | 0.3199 | benign | -0.647 | Destabilizing | 0.978 | D | 0.558 | neutral | None | None | None | None | I |
| R/I | 0.916 | likely_pathogenic | 0.9023 | pathogenic | 0.525 | Stabilizing | 0.97 | D | 0.677 | prob.neutral | N | 0.495442927 | None | None | I |
| R/K | 0.2413 | likely_benign | 0.2146 | benign | -0.122 | Destabilizing | 0.006 | N | 0.335 | neutral | N | 0.469757427 | None | None | I |
| R/L | 0.8103 | likely_pathogenic | 0.7808 | pathogenic | 0.525 | Stabilizing | 0.86 | D | 0.604 | neutral | None | None | None | None | I |
| R/M | 0.864 | likely_pathogenic | 0.8249 | pathogenic | -0.076 | Destabilizing | 0.998 | D | 0.587 | neutral | None | None | None | None | I |
| R/N | 0.9591 | likely_pathogenic | 0.9473 | pathogenic | -0.132 | Destabilizing | 0.956 | D | 0.551 | neutral | None | None | None | None | I |
| R/P | 0.8934 | likely_pathogenic | 0.8823 | pathogenic | 0.387 | Stabilizing | 0.978 | D | 0.667 | neutral | None | None | None | None | I |
| R/Q | 0.3732 | ambiguous | 0.3219 | benign | -0.125 | Destabilizing | 0.956 | D | 0.573 | neutral | None | None | None | None | I |
| R/S | 0.9634 | likely_pathogenic | 0.9563 | pathogenic | -0.375 | Destabilizing | 0.822 | D | 0.626 | neutral | N | 0.491387095 | None | None | I |
| R/T | 0.9014 | likely_pathogenic | 0.8834 | pathogenic | -0.158 | Destabilizing | 0.822 | D | 0.581 | neutral | D | 0.524399989 | None | None | I |
| R/V | 0.918 | likely_pathogenic | 0.9047 | pathogenic | 0.387 | Stabilizing | 0.956 | D | 0.667 | neutral | None | None | None | None | I |
| R/W | 0.7076 | likely_pathogenic | 0.6988 | pathogenic | -0.295 | Destabilizing | 0.998 | D | 0.702 | prob.neutral | None | None | None | None | I |
| R/Y | 0.8951 | likely_pathogenic | 0.8818 | pathogenic | 0.126 | Stabilizing | 0.993 | D | 0.671 | 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.