Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21856 | 65791;65792;65793 | chr2:178583616;178583615;178583614 | chr2:179448343;179448342;179448341 |
| N2AB | 20215 | 60868;60869;60870 | chr2:178583616;178583615;178583614 | chr2:179448343;179448342;179448341 |
| N2A | 19288 | 58087;58088;58089 | chr2:178583616;178583615;178583614 | chr2:179448343;179448342;179448341 |
| N2B | 12791 | 38596;38597;38598 | chr2:178583616;178583615;178583614 | chr2:179448343;179448342;179448341 |
| Novex-1 | 12916 | 38971;38972;38973 | chr2:178583616;178583615;178583614 | chr2:179448343;179448342;179448341 |
| Novex-2 | 12983 | 39172;39173;39174 | chr2:178583616;178583615;178583614 | chr2:179448343;179448342;179448341 |
| 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/T | rs752176305  |
-0.359 | 0.988 | N | 0.613 | 0.172 | 0.396494342077 | gnomAD-2.1.1 | 6.66E-05 | None | None | None | None | I | None | 0 | 3.01E-05 | None | 0 | 8.00641E-04 | None | 0 | None | 0 | 9.16E-06 | 0 |
| A/T | rs752176305 |
-0.359 | 0.988 | N | 0.613 | 0.172 | 0.396494342077 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 2.41E-05 | 6.56E-05 | 0 | 0 | 3.89105E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs752176305 |
-0.359 | 0.988 | N | 0.613 | 0.172 | 0.396494342077 | gnomAD-4.0.0 | 2.12921E-05 | None | None | None | None | I | None | 1.34073E-05 | 3.40437E-05 | None | 0 | 3.1607E-04 | None | 0 | 0 | 1.11175E-05 | 1.12562E-05 | 4.85909E-05 |
| A/V | rs1303979451 |
-0.05 | 0.935 | N | 0.644 | 0.183 | 0.437741185291 | gnomAD-2.1.1 | 4.15E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.45E-05 | None | 0 | 0 | 0 |
| A/V | rs1303979451 |
-0.05 | 0.935 | N | 0.644 | 0.183 | 0.437741185291 | gnomAD-4.0.0 | 2.76665E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.72251E-06 | 1.187E-05 | 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 | 0.6255 | likely_pathogenic | 0.5784 | pathogenic | -0.818 | Destabilizing | 0.999 | D | 0.604 | neutral | None | None | None | None | I |
| A/D | 0.3042 | likely_benign | 0.3222 | benign | -0.672 | Destabilizing | 0.943 | D | 0.424 | neutral | None | None | None | None | I |
| A/E | 0.2839 | likely_benign | 0.2935 | benign | -0.821 | Destabilizing | 0.18 | N | 0.383 | neutral | N | 0.476130747 | None | None | I |
| A/F | 0.6045 | likely_pathogenic | 0.5541 | ambiguous | -0.844 | Destabilizing | 0.995 | D | 0.623 | neutral | None | None | None | None | I |
| A/G | 0.192 | likely_benign | 0.1829 | benign | -0.264 | Destabilizing | 0.877 | D | 0.549 | neutral | N | 0.511686115 | None | None | I |
| A/H | 0.6331 | likely_pathogenic | 0.5952 | pathogenic | -0.25 | Destabilizing | 0.999 | D | 0.642 | neutral | None | None | None | None | I |
| A/I | 0.5444 | ambiguous | 0.4823 | ambiguous | -0.332 | Destabilizing | 0.985 | D | 0.588 | neutral | None | None | None | None | I |
| A/K | 0.6565 | likely_pathogenic | 0.6349 | pathogenic | -0.697 | Destabilizing | 0.971 | D | 0.601 | neutral | None | None | None | None | I |
| A/L | 0.3102 | likely_benign | 0.2667 | benign | -0.332 | Destabilizing | 0.904 | D | 0.623 | neutral | None | None | None | None | I |
| A/M | 0.4077 | ambiguous | 0.3566 | ambiguous | -0.527 | Destabilizing | 0.999 | D | 0.604 | neutral | None | None | None | None | I |
| A/N | 0.3662 | ambiguous | 0.3392 | benign | -0.36 | Destabilizing | 0.985 | D | 0.697 | prob.delet. | None | None | None | None | I |
| A/P | 0.1425 | likely_benign | 0.135 | benign | -0.267 | Destabilizing | 0.116 | N | 0.379 | neutral | N | 0.467012618 | None | None | I |
| A/Q | 0.418 | ambiguous | 0.4006 | ambiguous | -0.645 | Destabilizing | 0.971 | D | 0.594 | neutral | None | None | None | None | I |
| A/R | 0.5868 | likely_pathogenic | 0.5747 | pathogenic | -0.207 | Destabilizing | 0.971 | D | 0.593 | neutral | None | None | None | None | I |
| A/S | 0.1102 | likely_benign | 0.1099 | benign | -0.52 | Destabilizing | 0.947 | D | 0.574 | neutral | N | 0.505413504 | None | None | I |
| A/T | 0.1468 | likely_benign | 0.1398 | benign | -0.598 | Destabilizing | 0.988 | D | 0.613 | neutral | N | 0.512379549 | None | None | I |
| A/V | 0.2558 | likely_benign | 0.2283 | benign | -0.267 | Destabilizing | 0.935 | D | 0.644 | neutral | N | 0.468771437 | None | None | I |
| A/W | 0.862 | likely_pathogenic | 0.8299 | pathogenic | -0.97 | Destabilizing | 0.999 | D | 0.83 | deleterious | None | None | None | None | I |
| A/Y | 0.7015 | likely_pathogenic | 0.655 | pathogenic | -0.641 | Destabilizing | 0.995 | D | 0.622 | 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.