Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25466 | 76621;76622;76623 | chr2:178569736;178569735;178569734 | chr2:179434463;179434462;179434461 |
| N2AB | 23825 | 71698;71699;71700 | chr2:178569736;178569735;178569734 | chr2:179434463;179434462;179434461 |
| N2A | 22898 | 68917;68918;68919 | chr2:178569736;178569735;178569734 | chr2:179434463;179434462;179434461 |
| N2B | 16401 | 49426;49427;49428 | chr2:178569736;178569735;178569734 | chr2:179434463;179434462;179434461 |
| Novex-1 | 16526 | 49801;49802;49803 | chr2:178569736;178569735;178569734 | chr2:179434463;179434462;179434461 |
| Novex-2 | 16593 | 50002;50003;50004 | chr2:178569736;178569735;178569734 | chr2:179434463;179434462;179434461 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/K | rs780302234  |
None | 0.033 | N | 0.512 | 0.236 | 0.599449292227 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/K | rs780302234 |
None | 0.033 | N | 0.512 | 0.236 | 0.599449292227 | gnomAD-4.0.0 | 6.57851E-06 | None | None | None | None | N | None | 2.41488E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs780302234 |
-2.346 | None | N | 0.298 | 0.139 | 0.341934017632 | gnomAD-4.0.0 | 1.36887E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99572E-07 | 1.15966E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1726 | likely_benign | 0.137 | benign | -2.096 | Highly Destabilizing | 0.004 | N | 0.42 | neutral | None | None | None | None | N |
| I/C | 0.4211 | ambiguous | 0.3637 | ambiguous | -1.337 | Destabilizing | 0.497 | N | 0.514 | neutral | None | None | None | None | N |
| I/D | 0.602 | likely_pathogenic | 0.5249 | ambiguous | -2.107 | Highly Destabilizing | 0.044 | N | 0.557 | neutral | None | None | None | None | N |
| I/E | 0.4569 | ambiguous | 0.3771 | ambiguous | -1.909 | Destabilizing | 0.044 | N | 0.534 | neutral | None | None | None | None | N |
| I/F | 0.0768 | likely_benign | 0.0711 | benign | -1.151 | Destabilizing | None | N | 0.133 | neutral | None | None | None | None | N |
| I/G | 0.4746 | ambiguous | 0.3924 | ambiguous | -2.603 | Highly Destabilizing | 0.044 | N | 0.493 | neutral | None | None | None | None | N |
| I/H | 0.3254 | likely_benign | 0.2578 | benign | -1.905 | Destabilizing | 0.138 | N | 0.561 | neutral | None | None | None | None | N |
| I/K | 0.2547 | likely_benign | 0.1956 | benign | -1.664 | Destabilizing | 0.033 | N | 0.512 | neutral | N | 0.500895906 | None | None | N |
| I/L | 0.0639 | likely_benign | 0.0509 | benign | -0.664 | Destabilizing | None | N | 0.109 | neutral | N | 0.381663148 | None | None | N |
| I/M | 0.0554 | likely_benign | 0.0483 | benign | -0.568 | Destabilizing | None | N | 0.354 | neutral | N | 0.444175831 | None | None | N |
| I/N | 0.2967 | likely_benign | 0.252 | benign | -1.924 | Destabilizing | 0.044 | N | 0.582 | neutral | None | None | None | None | N |
| I/P | 0.8915 | likely_pathogenic | 0.7883 | pathogenic | -1.118 | Destabilizing | 0.085 | N | 0.605 | neutral | None | None | None | None | N |
| I/Q | 0.3106 | likely_benign | 0.2343 | benign | -1.817 | Destabilizing | 0.245 | N | 0.601 | neutral | None | None | None | None | N |
| I/R | 0.192 | likely_benign | 0.1401 | benign | -1.359 | Destabilizing | 0.033 | N | 0.581 | neutral | N | 0.500722547 | None | None | N |
| I/S | 0.2131 | likely_benign | 0.1805 | benign | -2.607 | Highly Destabilizing | 0.009 | N | 0.432 | neutral | None | None | None | None | N |
| I/T | 0.1081 | likely_benign | 0.0921 | benign | -2.263 | Highly Destabilizing | None | N | 0.298 | neutral | N | 0.425147353 | None | None | N |
| I/V | 0.064 | likely_benign | 0.0601 | benign | -1.118 | Destabilizing | None | N | 0.115 | neutral | N | 0.394320227 | None | None | N |
| I/W | 0.4646 | ambiguous | 0.3269 | benign | -1.475 | Destabilizing | 0.245 | N | 0.571 | neutral | None | None | None | None | N |
| I/Y | 0.2486 | likely_benign | 0.2046 | benign | -1.156 | Destabilizing | None | N | 0.275 | neutral | 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.