Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19605 | 59038;59039;59040 | chr2:178593395;178593394;178593393 | chr2:179458122;179458121;179458120 |
| N2AB | 17964 | 54115;54116;54117 | chr2:178593395;178593394;178593393 | chr2:179458122;179458121;179458120 |
| N2A | 17037 | 51334;51335;51336 | chr2:178593395;178593394;178593393 | chr2:179458122;179458121;179458120 |
| N2B | 10540 | 31843;31844;31845 | chr2:178593395;178593394;178593393 | chr2:179458122;179458121;179458120 |
| Novex-1 | 10665 | 32218;32219;32220 | chr2:178593395;178593394;178593393 | chr2:179458122;179458121;179458120 |
| Novex-2 | 10732 | 32419;32420;32421 | chr2:178593395;178593394;178593393 | chr2:179458122;179458121;179458120 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 1.0 | N | 0.759 | 0.494 | 0.547384771329 | gnomAD-4.0.0 | 1.59223E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43308E-05 | 0 |
| D/N | rs374833667  |
-0.468 | 1.0 | N | 0.727 | 0.372 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.55E-05 | 0 |
| D/N | rs374833667 |
-0.468 | 1.0 | N | 0.727 | 0.372 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| D/N | rs374833667 |
-0.468 | 1.0 | N | 0.727 | 0.372 | None | gnomAD-4.0.0 | 2.72742E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.30628E-05 | 1.09801E-05 | 6.40574E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8161 | likely_pathogenic | 0.814 | pathogenic | -0.251 | Destabilizing | 1.0 | D | 0.779 | deleterious | N | 0.501945435 | None | None | I |
| D/C | 0.9332 | likely_pathogenic | 0.9351 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| D/E | 0.7677 | likely_pathogenic | 0.7724 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.441 | neutral | N | 0.503235655 | None | None | I |
| D/F | 0.9717 | likely_pathogenic | 0.9729 | pathogenic | -0.345 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| D/G | 0.7232 | likely_pathogenic | 0.733 | pathogenic | -0.605 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.521570627 | None | None | I |
| D/H | 0.8229 | likely_pathogenic | 0.8221 | pathogenic | -0.976 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.502705904 | None | None | I |
| D/I | 0.9481 | likely_pathogenic | 0.9509 | pathogenic | 0.68 | Stabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| D/K | 0.9336 | likely_pathogenic | 0.9367 | pathogenic | -0.965 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| D/L | 0.9475 | likely_pathogenic | 0.9471 | pathogenic | 0.68 | Stabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| D/M | 0.9791 | likely_pathogenic | 0.9795 | pathogenic | 1.181 | Stabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| D/N | 0.245 | likely_benign | 0.2468 | benign | -1.181 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | N | 0.506611157 | None | None | I |
| D/P | 0.9548 | likely_pathogenic | 0.9581 | pathogenic | 0.396 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| D/Q | 0.9119 | likely_pathogenic | 0.9143 | pathogenic | -0.939 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| D/R | 0.924 | likely_pathogenic | 0.9247 | pathogenic | -1.026 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| D/S | 0.5099 | ambiguous | 0.4889 | ambiguous | -1.496 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | I |
| D/T | 0.7932 | likely_pathogenic | 0.8004 | pathogenic | -1.208 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| D/V | 0.8857 | likely_pathogenic | 0.8893 | pathogenic | 0.396 | Stabilizing | 1.0 | D | 0.784 | deleterious | D | 0.528696971 | None | None | I |
| D/W | 0.9914 | likely_pathogenic | 0.9923 | pathogenic | -0.549 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| D/Y | 0.7801 | likely_pathogenic | 0.8015 | pathogenic | -0.258 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | D | 0.529964418 | 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.