Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24043 | 72352;72353;72354 | chr2:178574005;178574004;178574003 | chr2:179438732;179438731;179438730 |
| N2AB | 22402 | 67429;67430;67431 | chr2:178574005;178574004;178574003 | chr2:179438732;179438731;179438730 |
| N2A | 21475 | 64648;64649;64650 | chr2:178574005;178574004;178574003 | chr2:179438732;179438731;179438730 |
| N2B | 14978 | 45157;45158;45159 | chr2:178574005;178574004;178574003 | chr2:179438732;179438731;179438730 |
| Novex-1 | 15103 | 45532;45533;45534 | chr2:178574005;178574004;178574003 | chr2:179438732;179438731;179438730 |
| Novex-2 | 15170 | 45733;45734;45735 | chr2:178574005;178574004;178574003 | chr2:179438732;179438731;179438730 |
| 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/S | rs760621388  |
-0.15 | 1.0 | N | 0.571 | 0.21 | 0.170165803431 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/S | rs760621388 |
-0.15 | 1.0 | N | 0.571 | 0.21 | 0.170165803431 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/S | rs760621388 |
-0.15 | 1.0 | N | 0.571 | 0.21 | 0.170165803431 | gnomAD-4.0.0 | 2.5636E-06 | None | None | None | None | I | None | 3.38398E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | None | None | 1.0 | N | 0.741 | 0.29 | 0.191931220699 | gnomAD-4.0.0 | 1.59219E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85943E-06 | 0 | 0 |
| A/V | None | None | 1.0 | N | 0.661 | 0.321 | 0.321108458156 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.7851 | likely_pathogenic | 0.7668 | pathogenic | -0.912 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| A/D | 0.8655 | likely_pathogenic | 0.8253 | pathogenic | -0.844 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | I |
| A/E | 0.7293 | likely_pathogenic | 0.6627 | pathogenic | -0.987 | Destabilizing | 1.0 | D | 0.772 | deleterious | N | 0.492318416 | None | None | I |
| A/F | 0.8224 | likely_pathogenic | 0.7975 | pathogenic | -1.169 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| A/G | 0.3324 | likely_benign | 0.291 | benign | -0.734 | Destabilizing | 1.0 | D | 0.563 | neutral | N | 0.509399449 | None | None | I |
| A/H | 0.8771 | likely_pathogenic | 0.8604 | pathogenic | -0.707 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| A/I | 0.6209 | likely_pathogenic | 0.6426 | pathogenic | -0.589 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | I |
| A/K | 0.8364 | likely_pathogenic | 0.7989 | pathogenic | -0.889 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| A/L | 0.6286 | likely_pathogenic | 0.6103 | pathogenic | -0.589 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| A/M | 0.5873 | likely_pathogenic | 0.5752 | pathogenic | -0.458 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| A/N | 0.7134 | likely_pathogenic | 0.6646 | pathogenic | -0.574 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| A/P | 0.8928 | likely_pathogenic | 0.8819 | pathogenic | -0.572 | Destabilizing | 1.0 | D | 0.773 | deleterious | N | 0.463529701 | None | None | I |
| A/Q | 0.6943 | likely_pathogenic | 0.6424 | pathogenic | -0.904 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| A/R | 0.7653 | likely_pathogenic | 0.7344 | pathogenic | -0.356 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | I |
| A/S | 0.1671 | likely_benign | 0.159 | benign | -0.81 | Destabilizing | 1.0 | D | 0.571 | neutral | N | 0.457528993 | None | None | I |
| A/T | 0.2925 | likely_benign | 0.2929 | benign | -0.877 | Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.467808888 | None | None | I |
| A/V | 0.2877 | likely_benign | 0.3065 | benign | -0.572 | Destabilizing | 1.0 | D | 0.661 | neutral | N | 0.508770735 | None | None | I |
| A/W | 0.9723 | likely_pathogenic | 0.9678 | pathogenic | -1.279 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | I |
| A/Y | 0.8818 | likely_pathogenic | 0.8633 | pathogenic | -0.948 | Destabilizing | 1.0 | D | 0.812 | deleterious | 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.