Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19198 | 57817;57818;57819 | chr2:178595762;178595761;178595760 | chr2:179460489;179460488;179460487 |
| N2AB | 17557 | 52894;52895;52896 | chr2:178595762;178595761;178595760 | chr2:179460489;179460488;179460487 |
| N2A | 16630 | 50113;50114;50115 | chr2:178595762;178595761;178595760 | chr2:179460489;179460488;179460487 |
| N2B | 10133 | 30622;30623;30624 | chr2:178595762;178595761;178595760 | chr2:179460489;179460488;179460487 |
| Novex-1 | 10258 | 30997;30998;30999 | chr2:178595762;178595761;178595760 | chr2:179460489;179460488;179460487 |
| Novex-2 | 10325 | 31198;31199;31200 | chr2:178595762;178595761;178595760 | chr2:179460489;179460488;179460487 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs367606284  |
0.129 | 0.062 | N | 0.295 | 0.119 | 0.0986583533028 | gnomAD-2.1.1 | 7.34E-06 | None | None | None | None | N | None | 8.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/K | rs367606284 |
0.129 | 0.062 | N | 0.295 | 0.119 | 0.0986583533028 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20773E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/K | rs367606284 |
0.129 | 0.062 | N | 0.295 | 0.119 | 0.0986583533028 | gnomAD-4.0.0 | 4.3507E-06 | None | None | None | None | N | None | 9.35579E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs199787097 |
-0.46 | None | N | 0.087 | 0.138 | None | gnomAD-2.1.1 | 3.74E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.35E-05 | 1.70882E-04 |
| N/S | rs199787097 |
-0.46 | None | N | 0.087 | 0.138 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| N/S | rs199787097 |
-0.46 | None | N | 0.087 | 0.138 | None | gnomAD-4.0.0 | 1.11276E-04 | None | None | None | None | N | None | 4.00941E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.452E-04 | 0 | 8.02878E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.124 | likely_benign | 0.1289 | benign | -0.6 | Destabilizing | 0.002 | N | 0.262 | neutral | None | None | None | None | N |
| N/C | 0.255 | likely_benign | 0.2348 | benign | 0.2 | Stabilizing | 0.824 | D | 0.498 | neutral | None | None | None | None | N |
| N/D | 0.1334 | likely_benign | 0.1571 | benign | -0.551 | Destabilizing | 0.062 | N | 0.373 | neutral | N | 0.426435432 | None | None | N |
| N/E | 0.2733 | likely_benign | 0.2992 | benign | -0.566 | Destabilizing | 0.081 | N | 0.3 | neutral | None | None | None | None | N |
| N/F | 0.4907 | ambiguous | 0.5192 | ambiguous | -0.825 | Destabilizing | 0.555 | D | 0.515 | neutral | None | None | None | None | N |
| N/G | 0.1901 | likely_benign | 0.195 | benign | -0.81 | Destabilizing | 0.035 | N | 0.357 | neutral | None | None | None | None | N |
| N/H | 0.1239 | likely_benign | 0.1177 | benign | -0.793 | Destabilizing | 0.484 | N | 0.367 | neutral | N | 0.484561016 | None | None | N |
| N/I | 0.1838 | likely_benign | 0.1987 | benign | -0.118 | Destabilizing | 0.317 | N | 0.524 | neutral | N | 0.495682087 | None | None | N |
| N/K | 0.2377 | likely_benign | 0.206 | benign | -0.086 | Destabilizing | 0.062 | N | 0.295 | neutral | N | 0.394267086 | None | None | N |
| N/L | 0.1837 | likely_benign | 0.2037 | benign | -0.118 | Destabilizing | 0.149 | N | 0.489 | neutral | None | None | None | None | N |
| N/M | 0.2481 | likely_benign | 0.2647 | benign | 0.501 | Stabilizing | 0.935 | D | 0.461 | neutral | None | None | None | None | N |
| N/P | 0.2577 | likely_benign | 0.3425 | ambiguous | -0.252 | Destabilizing | 0.38 | N | 0.495 | neutral | None | None | None | None | N |
| N/Q | 0.2693 | likely_benign | 0.2713 | benign | -0.769 | Destabilizing | 0.38 | N | 0.369 | neutral | None | None | None | None | N |
| N/R | 0.2692 | likely_benign | 0.258 | benign | 0.096 | Stabilizing | 0.38 | N | 0.35 | neutral | None | None | None | None | N |
| N/S | 0.0663 | likely_benign | 0.0686 | benign | -0.431 | Destabilizing | None | N | 0.087 | neutral | N | 0.394744301 | None | None | N |
| N/T | 0.091 | likely_benign | 0.1029 | benign | -0.301 | Destabilizing | 0.002 | N | 0.199 | neutral | N | 0.46926349 | None | None | N |
| N/V | 0.16 | likely_benign | 0.1798 | benign | -0.252 | Destabilizing | 0.149 | N | 0.478 | neutral | None | None | None | None | N |
| N/W | 0.6897 | likely_pathogenic | 0.7095 | pathogenic | -0.677 | Destabilizing | 0.935 | D | 0.633 | neutral | None | None | None | None | N |
| N/Y | 0.1837 | likely_benign | 0.1848 | benign | -0.45 | Destabilizing | 0.484 | N | 0.488 | neutral | N | 0.514363848 | 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.