Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20542 | 61849;61850;61851 | chr2:178590101;178590100;178590099 | chr2:179454828;179454827;179454826 |
| N2AB | 18901 | 56926;56927;56928 | chr2:178590101;178590100;178590099 | chr2:179454828;179454827;179454826 |
| N2A | 17974 | 54145;54146;54147 | chr2:178590101;178590100;178590099 | chr2:179454828;179454827;179454826 |
| N2B | 11477 | 34654;34655;34656 | chr2:178590101;178590100;178590099 | chr2:179454828;179454827;179454826 |
| Novex-1 | 11602 | 35029;35030;35031 | chr2:178590101;178590100;178590099 | chr2:179454828;179454827;179454826 |
| Novex-2 | 11669 | 35230;35231;35232 | chr2:178590101;178590100;178590099 | chr2:179454828;179454827;179454826 |
| 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/G | rs373529637  |
-0.183 | 0.027 | N | 0.311 | 0.054 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 2.58465E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/G | rs373529637 |
-0.183 | 0.027 | N | 0.311 | 0.054 | None | gnomAD-3.1.2 | 7.24E-05 | None | None | None | None | I | None | 2.65572E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/G | rs373529637 |
-0.183 | 0.027 | N | 0.311 | 0.054 | None | gnomAD-4.0.0 | 9.29896E-06 | None | None | None | None | I | None | 2.00363E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs373529637 |
-0.072 | 0.062 | N | 0.286 | 0.1 | 0.201204373187 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs373529637 |
-0.072 | 0.062 | N | 0.286 | 0.1 | 0.201204373187 | gnomAD-4.0.0 | 2.0533E-06 | None | None | None | None | I | None | 0 | 6.71381E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.4198 | ambiguous | 0.4661 | ambiguous | -0.678 | Destabilizing | 0.824 | D | 0.329 | neutral | None | None | None | None | I |
| A/D | 0.2005 | likely_benign | 0.2307 | benign | -1.115 | Destabilizing | None | N | 0.261 | neutral | N | 0.430136593 | None | None | I |
| A/E | 0.1771 | likely_benign | 0.198 | benign | -1.265 | Destabilizing | 0.081 | N | 0.296 | neutral | None | None | None | None | I |
| A/F | 0.3746 | ambiguous | 0.426 | ambiguous | -1.116 | Destabilizing | 0.555 | D | 0.397 | neutral | None | None | None | None | I |
| A/G | 0.1123 | likely_benign | 0.1255 | benign | -0.647 | Destabilizing | 0.027 | N | 0.311 | neutral | N | 0.454784322 | None | None | I |
| A/H | 0.4214 | ambiguous | 0.4755 | ambiguous | -0.702 | Destabilizing | 0.824 | D | 0.389 | neutral | None | None | None | None | I |
| A/I | 0.2485 | likely_benign | 0.2839 | benign | -0.536 | Destabilizing | 0.235 | N | 0.316 | neutral | None | None | None | None | I |
| A/K | 0.3541 | ambiguous | 0.4006 | ambiguous | -1.052 | Destabilizing | 0.081 | N | 0.328 | neutral | None | None | None | None | I |
| A/L | 0.1593 | likely_benign | 0.1823 | benign | -0.536 | Destabilizing | 0.081 | N | 0.276 | neutral | None | None | None | None | I |
| A/M | 0.2151 | likely_benign | 0.2483 | benign | -0.393 | Destabilizing | 0.824 | D | 0.337 | neutral | None | None | None | None | I |
| A/N | 0.1743 | likely_benign | 0.1963 | benign | -0.61 | Destabilizing | 0.081 | N | 0.327 | neutral | None | None | None | None | I |
| A/P | 0.3379 | likely_benign | 0.3997 | ambiguous | -0.512 | Destabilizing | 0.317 | N | 0.315 | neutral | N | 0.455451851 | None | None | I |
| A/Q | 0.2709 | likely_benign | 0.3006 | benign | -0.942 | Destabilizing | 0.38 | N | 0.331 | neutral | None | None | None | None | I |
| A/R | 0.3506 | ambiguous | 0.3901 | ambiguous | -0.446 | Destabilizing | 0.38 | N | 0.331 | neutral | None | None | None | None | I |
| A/S | 0.0821 | likely_benign | 0.0865 | benign | -0.743 | Destabilizing | None | N | 0.197 | neutral | N | 0.418783449 | None | None | I |
| A/T | 0.085 | likely_benign | 0.0925 | benign | -0.831 | Destabilizing | None | N | 0.289 | neutral | N | 0.467174829 | None | None | I |
| A/V | 0.1359 | likely_benign | 0.154 | benign | -0.512 | Destabilizing | 0.062 | N | 0.286 | neutral | N | 0.453236579 | None | None | I |
| A/W | 0.6993 | likely_pathogenic | 0.7586 | pathogenic | -1.273 | Destabilizing | 0.935 | D | 0.549 | neutral | None | None | None | None | I |
| A/Y | 0.4844 | ambiguous | 0.5457 | ambiguous | -0.962 | Destabilizing | 0.555 | D | 0.397 | 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.