Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24544 | 73855;73856;73857 | chr2:178572502;178572501;178572500 | chr2:179437229;179437228;179437227 |
| N2AB | 22903 | 68932;68933;68934 | chr2:178572502;178572501;178572500 | chr2:179437229;179437228;179437227 |
| N2A | 21976 | 66151;66152;66153 | chr2:178572502;178572501;178572500 | chr2:179437229;179437228;179437227 |
| N2B | 15479 | 46660;46661;46662 | chr2:178572502;178572501;178572500 | chr2:179437229;179437228;179437227 |
| Novex-1 | 15604 | 47035;47036;47037 | chr2:178572502;178572501;178572500 | chr2:179437229;179437228;179437227 |
| Novex-2 | 15671 | 47236;47237;47238 | chr2:178572502;178572501;178572500 | chr2:179437229;179437228;179437227 |
| 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/F | rs777417650  |
-0.579 | 0.984 | N | 0.554 | 0.336 | 0.509878532422 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.56E-05 | 0 |
| L/F | rs777417650 |
-0.579 | 0.984 | N | 0.554 | 0.336 | 0.509878532422 | 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 |
| L/F | rs777417650 |
-0.579 | 0.984 | N | 0.554 | 0.336 | 0.509878532422 | gnomAD-4.0.0 | 2.29354E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88238E-05 | 0 | 4.80492E-05 |
| L/V | None | None | 0.011 | N | 0.264 | 0.15 | 0.277317399466 | gnomAD-4.0.0 | 6.84397E-07 | None | None | None | None | I | None | 2.98972E-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 | 0.1635 | likely_benign | 0.144 | benign | -0.533 | Destabilizing | 0.967 | D | 0.547 | neutral | None | None | None | None | I |
| L/C | 0.4813 | ambiguous | 0.4126 | ambiguous | -0.629 | Destabilizing | 1.0 | D | 0.571 | neutral | None | None | None | None | I |
| L/D | 0.5879 | likely_pathogenic | 0.5132 | ambiguous | -0.278 | Destabilizing | 0.995 | D | 0.688 | prob.neutral | None | None | None | None | I |
| L/E | 0.3032 | likely_benign | 0.2681 | benign | -0.369 | Destabilizing | 0.994 | D | 0.697 | prob.neutral | None | None | None | None | I |
| L/F | 0.1537 | likely_benign | 0.134 | benign | -0.57 | Destabilizing | 0.984 | D | 0.554 | neutral | N | 0.511096014 | None | None | I |
| L/G | 0.4216 | ambiguous | 0.3649 | ambiguous | -0.68 | Destabilizing | 0.995 | D | 0.699 | prob.neutral | None | None | None | None | I |
| L/H | 0.2254 | likely_benign | 0.2042 | benign | 0.05 | Stabilizing | 0.999 | D | 0.68 | prob.neutral | N | 0.475812556 | None | None | I |
| L/I | 0.0757 | likely_benign | 0.072 | benign | -0.266 | Destabilizing | 0.246 | N | 0.493 | neutral | N | 0.473247944 | None | None | I |
| L/K | 0.2521 | likely_benign | 0.2456 | benign | -0.349 | Destabilizing | 0.86 | D | 0.645 | neutral | None | None | None | None | I |
| L/M | 0.1069 | likely_benign | 0.1029 | benign | -0.446 | Destabilizing | 0.962 | D | 0.555 | neutral | None | None | None | None | I |
| L/N | 0.2858 | likely_benign | 0.2512 | benign | -0.159 | Destabilizing | 0.995 | D | 0.693 | prob.neutral | None | None | None | None | I |
| L/P | 0.321 | likely_benign | 0.2495 | benign | -0.323 | Destabilizing | 0.998 | D | 0.694 | prob.neutral | D | 0.522692543 | None | None | I |
| L/Q | 0.1334 | likely_benign | 0.1271 | benign | -0.374 | Destabilizing | 0.996 | D | 0.634 | neutral | None | None | None | None | I |
| L/R | 0.2229 | likely_benign | 0.2065 | benign | 0.2 | Stabilizing | 0.984 | D | 0.639 | neutral | N | 0.517036007 | None | None | I |
| L/S | 0.1867 | likely_benign | 0.16 | benign | -0.568 | Destabilizing | 0.981 | D | 0.526 | neutral | None | None | None | None | I |
| L/T | 0.1688 | likely_benign | 0.1488 | benign | -0.552 | Destabilizing | 0.215 | N | 0.319 | neutral | None | None | None | None | I |
| L/V | 0.0762 | likely_benign | 0.0742 | benign | -0.323 | Destabilizing | 0.011 | N | 0.264 | neutral | N | 0.467071334 | None | None | I |
| L/W | 0.3491 | ambiguous | 0.2957 | benign | -0.589 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| L/Y | 0.3289 | likely_benign | 0.2917 | benign | -0.347 | Destabilizing | 0.967 | D | 0.585 | 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.