Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26831 | 80716;80717;80718 | chr2:178565641;178565640;178565639 | chr2:179430368;179430367;179430366 |
| N2AB | 25190 | 75793;75794;75795 | chr2:178565641;178565640;178565639 | chr2:179430368;179430367;179430366 |
| N2A | 24263 | 73012;73013;73014 | chr2:178565641;178565640;178565639 | chr2:179430368;179430367;179430366 |
| N2B | 17766 | 53521;53522;53523 | chr2:178565641;178565640;178565639 | chr2:179430368;179430367;179430366 |
| Novex-1 | 17891 | 53896;53897;53898 | chr2:178565641;178565640;178565639 | chr2:179430368;179430367;179430366 |
| Novex-2 | 17958 | 54097;54098;54099 | chr2:178565641;178565640;178565639 | chr2:179430368;179430367;179430366 |
| 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/S | None | None | 0.014 | N | 0.263 | 0.032 | 0.128392430309 | gnomAD-4.0.0 | 6.84277E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99564E-07 | 0 | 0 |
| A/T | rs747404761  |
-0.865 | 0.012 | N | 0.182 | 0.031 | 0.148003135375 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| A/T | rs747404761 |
-0.865 | 0.012 | N | 0.182 | 0.031 | 0.148003135375 | gnomAD-4.0.0 | 6.84277E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99564E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3483 | ambiguous | 0.3668 | ambiguous | -0.834 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | I |
| A/D | 0.4663 | ambiguous | 0.4134 | ambiguous | -0.884 | Destabilizing | 0.98 | D | 0.603 | neutral | N | 0.510302036 | None | None | I |
| A/E | 0.4036 | ambiguous | 0.3627 | ambiguous | -0.911 | Destabilizing | 0.964 | D | 0.577 | neutral | None | None | None | None | I |
| A/F | 0.3635 | ambiguous | 0.3422 | ambiguous | -0.812 | Destabilizing | 0.998 | D | 0.661 | neutral | None | None | None | None | I |
| A/G | 0.1503 | likely_benign | 0.1417 | benign | -0.987 | Destabilizing | 0.41 | N | 0.495 | neutral | N | 0.492929783 | None | None | I |
| A/H | 0.5054 | ambiguous | 0.5102 | ambiguous | -1.187 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| A/I | 0.2725 | likely_benign | 0.2401 | benign | -0.205 | Destabilizing | 0.996 | D | 0.605 | neutral | None | None | None | None | I |
| A/K | 0.5204 | ambiguous | 0.5033 | ambiguous | -1.114 | Destabilizing | 0.986 | D | 0.577 | neutral | None | None | None | None | I |
| A/L | 0.1716 | likely_benign | 0.1643 | benign | -0.205 | Destabilizing | 0.972 | D | 0.515 | neutral | None | None | None | None | I |
| A/M | 0.1807 | likely_benign | 0.1679 | benign | -0.257 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | I |
| A/N | 0.3465 | ambiguous | 0.3094 | benign | -0.865 | Destabilizing | 0.886 | D | 0.608 | neutral | None | None | None | None | I |
| A/P | 0.8896 | likely_pathogenic | 0.8703 | pathogenic | -0.339 | Destabilizing | 0.99 | D | 0.609 | neutral | D | 0.523559335 | None | None | I |
| A/Q | 0.4032 | ambiguous | 0.397 | ambiguous | -0.987 | Destabilizing | 0.998 | D | 0.639 | neutral | None | None | None | None | I |
| A/R | 0.4709 | ambiguous | 0.4721 | ambiguous | -0.829 | Destabilizing | 0.996 | D | 0.625 | neutral | None | None | None | None | I |
| A/S | 0.1047 | likely_benign | 0.0962 | benign | -1.212 | Destabilizing | 0.014 | N | 0.263 | neutral | N | 0.484864873 | None | None | I |
| A/T | 0.074 | likely_benign | 0.0686 | benign | -1.142 | Destabilizing | 0.012 | N | 0.182 | neutral | N | 0.462526732 | None | None | I |
| A/V | 0.1365 | likely_benign | 0.1204 | benign | -0.339 | Destabilizing | 0.909 | D | 0.493 | neutral | N | 0.484424943 | None | None | I |
| A/W | 0.7391 | likely_pathogenic | 0.7358 | pathogenic | -1.176 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| A/Y | 0.496 | ambiguous | 0.4881 | ambiguous | -0.75 | Destabilizing | 0.999 | D | 0.666 | 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.