Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13761 | 41506;41507;41508 | chr2:178636446;178636445;178636444 | chr2:179501173;179501172;179501171 |
| N2AB | 12120 | 36583;36584;36585 | chr2:178636446;178636445;178636444 | chr2:179501173;179501172;179501171 |
| N2A | 11193 | 33802;33803;33804 | chr2:178636446;178636445;178636444 | chr2:179501173;179501172;179501171 |
| N2B | 4696 | 14311;14312;14313 | chr2:178636446;178636445;178636444 | chr2:179501173;179501172;179501171 |
| Novex-1 | 4821 | 14686;14687;14688 | chr2:178636446;178636445;178636444 | chr2:179501173;179501172;179501171 |
| Novex-2 | 4888 | 14887;14888;14889 | chr2:178636446;178636445;178636444 | chr2:179501173;179501172;179501171 |
| 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/C | rs376166350  |
None | 0.998 | D | 0.555 | 0.376 | None | gnomAD-4.0.0 | 2.05442E-06 | None | None | None | None | I | None | 2.99312E-05 | 0 | None | 0 | 2.52908E-05 | None | 0 | 0 | 0 | 1.16217E-05 | 0 |
| R/H | rs781139091 |
-0.844 | 0.98 | N | 0.573 | 0.284 | 0.311387274539 | gnomAD-2.1.1 | 3.95E-05 | None | None | None | None | I | None | 4.14E-05 | 0 | None | 0 | 5.17E-05 | None | 1.31648E-04 | None | 0 | 3.14E-05 | 1.41243E-04 |
| R/H | rs781139091 |
-0.844 | 0.98 | N | 0.573 | 0.284 | 0.311387274539 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14079E-04 | 0 |
| R/H | rs781139091 |
-0.844 | 0.98 | N | 0.573 | 0.284 | 0.311387274539 | gnomAD-4.0.0 | 2.7913E-05 | None | None | None | None | I | None | 1.33636E-05 | 1.66978E-05 | None | 0 | 4.47507E-05 | None | 0 | 0 | 1.61148E-05 | 2.09182E-04 | 4.80846E-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 | 0.9006 | likely_pathogenic | 0.9225 | pathogenic | -1.192 | Destabilizing | 0.25 | N | 0.494 | neutral | None | None | None | None | I |
| R/C | 0.5988 | likely_pathogenic | 0.6436 | pathogenic | -1.152 | Destabilizing | 0.998 | D | 0.555 | neutral | D | 0.637495836 | None | None | I |
| R/D | 0.9771 | likely_pathogenic | 0.982 | pathogenic | -0.218 | Destabilizing | 0.617 | D | 0.542 | neutral | None | None | None | None | I |
| R/E | 0.8738 | likely_pathogenic | 0.8976 | pathogenic | -0.103 | Destabilizing | 0.25 | N | 0.49 | neutral | None | None | None | None | I |
| R/F | 0.925 | likely_pathogenic | 0.9381 | pathogenic | -1.08 | Destabilizing | 0.972 | D | 0.537 | neutral | None | None | None | None | I |
| R/G | 0.8444 | likely_pathogenic | 0.8823 | pathogenic | -1.489 | Destabilizing | 0.756 | D | 0.575 | neutral | N | 0.500266614 | None | None | I |
| R/H | 0.2165 | likely_benign | 0.232 | benign | -1.584 | Destabilizing | 0.98 | D | 0.573 | neutral | N | 0.507578702 | None | None | I |
| R/I | 0.7572 | likely_pathogenic | 0.776 | pathogenic | -0.389 | Destabilizing | 0.92 | D | 0.547 | neutral | None | None | None | None | I |
| R/K | 0.1681 | likely_benign | 0.1747 | benign | -1.165 | Destabilizing | 0.001 | N | 0.218 | neutral | None | None | None | None | I |
| R/L | 0.6877 | likely_pathogenic | 0.7187 | pathogenic | -0.389 | Destabilizing | 0.756 | D | 0.575 | neutral | D | 0.536988271 | None | None | I |
| R/M | 0.7713 | likely_pathogenic | 0.7993 | pathogenic | -0.597 | Destabilizing | 0.972 | D | 0.522 | neutral | None | None | None | None | I |
| R/N | 0.9263 | likely_pathogenic | 0.9402 | pathogenic | -0.532 | Destabilizing | 0.617 | D | 0.555 | neutral | None | None | None | None | I |
| R/P | 0.9909 | likely_pathogenic | 0.9927 | pathogenic | -0.638 | Destabilizing | 0.957 | D | 0.54 | neutral | D | 0.636966338 | None | None | I |
| R/Q | 0.2424 | likely_benign | 0.2815 | benign | -0.788 | Destabilizing | 0.447 | N | 0.582 | neutral | None | None | None | None | I |
| R/S | 0.8967 | likely_pathogenic | 0.9185 | pathogenic | -1.44 | Destabilizing | 0.608 | D | 0.553 | neutral | N | 0.475967614 | None | None | I |
| R/T | 0.7387 | likely_pathogenic | 0.7778 | pathogenic | -1.149 | Destabilizing | 0.617 | D | 0.551 | neutral | None | None | None | None | I |
| R/V | 0.7882 | likely_pathogenic | 0.8081 | pathogenic | -0.638 | Destabilizing | 0.85 | D | 0.527 | neutral | None | None | None | None | I |
| R/W | 0.6213 | likely_pathogenic | 0.6564 | pathogenic | -0.643 | Destabilizing | 0.992 | D | 0.603 | neutral | None | None | None | None | I |
| R/Y | 0.8361 | likely_pathogenic | 0.862 | pathogenic | -0.372 | Destabilizing | 0.972 | D | 0.556 | 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.