Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21332 | 64219;64220;64221 | chr2:178587217;178587216;178587215 | chr2:179451944;179451943;179451942 |
| N2AB | 19691 | 59296;59297;59298 | chr2:178587217;178587216;178587215 | chr2:179451944;179451943;179451942 |
| N2A | 18764 | 56515;56516;56517 | chr2:178587217;178587216;178587215 | chr2:179451944;179451943;179451942 |
| N2B | 12267 | 37024;37025;37026 | chr2:178587217;178587216;178587215 | chr2:179451944;179451943;179451942 |
| Novex-1 | 12392 | 37399;37400;37401 | chr2:178587217;178587216;178587215 | chr2:179451944;179451943;179451942 |
| Novex-2 | 12459 | 37600;37601;37602 | chr2:178587217;178587216;178587215 | chr2:179451944;179451943;179451942 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.942 | N | 0.637 | 0.553 | 0.622959606287 | gnomAD-4.0.0 | 1.59227E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86049E-06 | 0 | 0 |
| P/S | None | None | 0.126 | N | 0.293 | 0.437 | 0.270447802918 | gnomAD-4.0.0 | 1.3688E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99682E-07 | 0 | 1.65733E-05 |
| P/T | rs879031561  |
-0.88 | 0.698 | N | 0.491 | 0.511 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 1.93849E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs879031561 |
-0.88 | 0.698 | N | 0.491 | 0.511 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 1.44921E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs879031561 |
-0.88 | 0.698 | N | 0.491 | 0.511 | None | gnomAD-4.0.0 | 1.11587E-05 | None | None | None | None | N | None | 1.60351E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09806E-05 | 8.00974E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.098 | likely_benign | 0.0961 | benign | -0.884 | Destabilizing | 0.698 | D | 0.387 | neutral | N | 0.486426798 | None | None | N |
| P/C | 0.6644 | likely_pathogenic | 0.6423 | pathogenic | -0.694 | Destabilizing | 0.998 | D | 0.701 | prob.neutral | None | None | None | None | N |
| P/D | 0.7792 | likely_pathogenic | 0.7276 | pathogenic | -0.677 | Destabilizing | 0.956 | D | 0.485 | neutral | None | None | None | None | N |
| P/E | 0.4524 | ambiguous | 0.4066 | ambiguous | -0.783 | Destabilizing | 0.754 | D | 0.499 | neutral | None | None | None | None | N |
| P/F | 0.7254 | likely_pathogenic | 0.6954 | pathogenic | -1.02 | Destabilizing | 0.994 | D | 0.705 | prob.neutral | None | None | None | None | N |
| P/G | 0.4645 | ambiguous | 0.46 | ambiguous | -1.058 | Destabilizing | 0.754 | D | 0.534 | neutral | None | None | None | None | N |
| P/H | 0.4296 | ambiguous | 0.3798 | ambiguous | -0.554 | Destabilizing | 0.992 | D | 0.623 | neutral | N | 0.509409806 | None | None | N |
| P/I | 0.4938 | ambiguous | 0.4606 | ambiguous | -0.563 | Destabilizing | 0.978 | D | 0.715 | prob.delet. | None | None | None | None | N |
| P/K | 0.6579 | likely_pathogenic | 0.573 | pathogenic | -0.694 | Destabilizing | 0.754 | D | 0.503 | neutral | None | None | None | None | N |
| P/L | 0.236 | likely_benign | 0.2119 | benign | -0.563 | Destabilizing | 0.942 | D | 0.637 | neutral | N | 0.497800012 | None | None | N |
| P/M | 0.4614 | ambiguous | 0.4536 | ambiguous | -0.388 | Destabilizing | 0.998 | D | 0.619 | neutral | None | None | None | None | N |
| P/N | 0.6199 | likely_pathogenic | 0.5805 | pathogenic | -0.411 | Destabilizing | 0.915 | D | 0.617 | neutral | None | None | None | None | N |
| P/Q | 0.2951 | likely_benign | 0.2678 | benign | -0.705 | Destabilizing | 0.356 | N | 0.357 | neutral | None | None | None | None | N |
| P/R | 0.4985 | ambiguous | 0.4128 | ambiguous | -0.073 | Destabilizing | 0.942 | D | 0.634 | neutral | N | 0.506434065 | None | None | N |
| P/S | 0.2191 | likely_benign | 0.2029 | benign | -0.81 | Destabilizing | 0.126 | N | 0.293 | neutral | N | 0.496786053 | None | None | N |
| P/T | 0.1788 | likely_benign | 0.1669 | benign | -0.817 | Destabilizing | 0.698 | D | 0.491 | neutral | N | 0.519495601 | None | None | N |
| P/V | 0.3238 | likely_benign | 0.2983 | benign | -0.634 | Destabilizing | 0.956 | D | 0.574 | neutral | None | None | None | None | N |
| P/W | 0.8452 | likely_pathogenic | 0.8063 | pathogenic | -1.077 | Destabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | N |
| P/Y | 0.7208 | likely_pathogenic | 0.6669 | pathogenic | -0.794 | Destabilizing | 0.993 | D | 0.713 | prob.delet. | None | None | 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.