Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14536 | 43831;43832;43833 | chr2:178632288;178632287;178632286 | chr2:179497015;179497014;179497013 |
| N2AB | 12895 | 38908;38909;38910 | chr2:178632288;178632287;178632286 | chr2:179497015;179497014;179497013 |
| N2A | 11968 | 36127;36128;36129 | chr2:178632288;178632287;178632286 | chr2:179497015;179497014;179497013 |
| N2B | 5471 | 16636;16637;16638 | chr2:178632288;178632287;178632286 | chr2:179497015;179497014;179497013 |
| Novex-1 | 5596 | 17011;17012;17013 | chr2:178632288;178632287;178632286 | chr2:179497015;179497014;179497013 |
| Novex-2 | 5663 | 17212;17213;17214 | chr2:178632288;178632287;178632286 | chr2:179497015;179497014;179497013 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs1405325105  |
-0.988 | 0.971 | D | 0.753 | 0.75 | 0.883407034073 | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.6909E-04 |
| L/P | rs1405325105 |
-0.988 | 0.971 | D | 0.753 | 0.75 | 0.883407034073 | gnomAD-4.0.0 | 1.60113E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03711E-05 |
| L/Q | rs1405325105 |
None | 0.247 | D | 0.441 | 0.638 | 0.82775553445 | gnomAD-4.0.0 | 1.60113E-06 | None | None | None | None | N | None | 5.67344E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8507 | likely_pathogenic | 0.7997 | pathogenic | -2.428 | Highly Destabilizing | 0.754 | D | 0.477 | neutral | None | None | None | None | N |
| L/C | 0.8759 | likely_pathogenic | 0.8146 | pathogenic | -1.42 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| L/D | 0.9872 | likely_pathogenic | 0.9834 | pathogenic | -2.768 | Highly Destabilizing | 0.956 | D | 0.735 | prob.delet. | None | None | None | None | N |
| L/E | 0.912 | likely_pathogenic | 0.8814 | pathogenic | -2.573 | Highly Destabilizing | 0.915 | D | 0.687 | prob.neutral | None | None | None | None | N |
| L/F | 0.4053 | ambiguous | 0.3162 | benign | -1.595 | Destabilizing | 0.978 | D | 0.595 | neutral | None | None | None | None | N |
| L/G | 0.9546 | likely_pathogenic | 0.9416 | pathogenic | -2.905 | Highly Destabilizing | 0.956 | D | 0.732 | prob.delet. | None | None | None | None | N |
| L/H | 0.8132 | likely_pathogenic | 0.7538 | pathogenic | -2.2 | Highly Destabilizing | 0.994 | D | 0.737 | prob.delet. | None | None | None | None | N |
| L/I | 0.1339 | likely_benign | 0.1133 | benign | -1.057 | Destabilizing | 0.126 | N | 0.303 | neutral | N | 0.509664248 | None | None | N |
| L/K | 0.8361 | likely_pathogenic | 0.797 | pathogenic | -1.863 | Destabilizing | 0.915 | D | 0.66 | neutral | None | None | None | None | N |
| L/M | 0.2622 | likely_benign | 0.2252 | benign | -0.781 | Destabilizing | 0.978 | D | 0.635 | neutral | None | None | None | None | N |
| L/N | 0.9428 | likely_pathogenic | 0.9255 | pathogenic | -2.128 | Highly Destabilizing | 0.956 | D | 0.747 | deleterious | None | None | None | None | N |
| L/P | 0.9344 | likely_pathogenic | 0.9172 | pathogenic | -1.496 | Destabilizing | 0.971 | D | 0.753 | deleterious | D | 0.681270734 | None | None | N |
| L/Q | 0.7148 | likely_pathogenic | 0.6398 | pathogenic | -2.078 | Highly Destabilizing | 0.247 | N | 0.441 | neutral | D | 0.681701296 | None | None | N |
| L/R | 0.7638 | likely_pathogenic | 0.7061 | pathogenic | -1.479 | Destabilizing | 0.89 | D | 0.701 | prob.neutral | D | 0.681270734 | None | None | N |
| L/S | 0.9205 | likely_pathogenic | 0.8973 | pathogenic | -2.738 | Highly Destabilizing | 0.915 | D | 0.643 | neutral | None | None | None | None | N |
| L/T | 0.8378 | likely_pathogenic | 0.8012 | pathogenic | -2.408 | Highly Destabilizing | 0.956 | D | 0.641 | neutral | None | None | None | None | N |
| L/V | 0.2223 | likely_benign | 0.1801 | benign | -1.496 | Destabilizing | 0.489 | N | 0.463 | neutral | N | 0.52126285 | None | None | N |
| L/W | 0.6387 | likely_pathogenic | 0.5683 | pathogenic | -1.928 | Destabilizing | 0.998 | D | 0.686 | prob.neutral | None | None | None | None | N |
| L/Y | 0.7915 | likely_pathogenic | 0.7172 | pathogenic | -1.62 | Destabilizing | 0.978 | D | 0.709 | 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.