Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35652 | 107179;107180;107181 | chr2:178528797;178528796;178528795 | chr2:179393524;179393523;179393522 |
| N2AB | 34011 | 102256;102257;102258 | chr2:178528797;178528796;178528795 | chr2:179393524;179393523;179393522 |
| N2A | 33084 | 99475;99476;99477 | chr2:178528797;178528796;178528795 | chr2:179393524;179393523;179393522 |
| N2B | 26587 | 79984;79985;79986 | chr2:178528797;178528796;178528795 | chr2:179393524;179393523;179393522 |
| Novex-1 | 26712 | 80359;80360;80361 | chr2:178528797;178528796;178528795 | chr2:179393524;179393523;179393522 |
| Novex-2 | 26779 | 80560;80561;80562 | chr2:178528797;178528796;178528795 | chr2:179393524;179393523;179393522 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs565675340  |
-1.547 | 0.922 | N | 0.527 | 0.385 | 0.403609169532 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.66E-05 | 0 | 0 |
| R/G | rs565675340 |
-1.547 | 0.922 | N | 0.527 | 0.385 | 0.403609169532 | gnomAD-4.0.0 | 1.369E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87427E-05 | 0 | 0 | 0 | 1.65739E-05 |
| R/Q | rs200497615 |
-0.477 | 0.447 | N | 0.315 | 0.111 | None | gnomAD-2.1.1 | 1.64394E-04 | None | None | None | None | N | None | 4.14E-05 | 5.68E-05 | None | 9.7E-05 | 0 | None | 2.94831E-04 | None | 0 | 2.57708E-04 | 0 |
| R/Q | rs200497615 |
-0.477 | 0.447 | N | 0.315 | 0.111 | None | gnomAD-3.1.2 | 1.70862E-04 | None | None | None | None | N | None | 1.20645E-04 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.93971E-04 | 0 | 0 |
| R/Q | rs200497615 |
-0.477 | 0.447 | N | 0.315 | 0.111 | None | gnomAD-4.0.0 | 3.97383E-04 | None | None | None | None | N | None | 9.3438E-05 | 6.67134E-05 | None | 3.38135E-05 | 0 | None | 1.56353E-05 | 1.64528E-04 | 5.03684E-04 | 2.85582E-04 | 1.12122E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6171 | likely_pathogenic | 0.5976 | pathogenic | -0.842 | Destabilizing | 0.754 | D | 0.527 | neutral | None | None | None | None | N |
| R/C | 0.2967 | likely_benign | 0.2741 | benign | -0.745 | Destabilizing | 0.998 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/D | 0.8356 | likely_pathogenic | 0.8376 | pathogenic | -0.16 | Destabilizing | 0.956 | D | 0.577 | neutral | None | None | None | None | N |
| R/E | 0.5569 | ambiguous | 0.5443 | ambiguous | -0.067 | Destabilizing | 0.754 | D | 0.488 | neutral | None | None | None | None | N |
| R/F | 0.7018 | likely_pathogenic | 0.6974 | pathogenic | -0.88 | Destabilizing | 0.993 | D | 0.682 | prob.neutral | None | None | None | None | N |
| R/G | 0.4647 | ambiguous | 0.4748 | ambiguous | -1.116 | Destabilizing | 0.922 | D | 0.527 | neutral | N | 0.484748309 | None | None | N |
| R/H | 0.1387 | likely_benign | 0.133 | benign | -1.355 | Destabilizing | 0.956 | D | 0.591 | neutral | None | None | None | None | N |
| R/I | 0.3437 | ambiguous | 0.3337 | benign | -0.114 | Destabilizing | 0.978 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/K | 0.1952 | likely_benign | 0.1833 | benign | -0.85 | Destabilizing | 0.559 | D | 0.48 | neutral | None | None | None | None | N |
| R/L | 0.3985 | ambiguous | 0.3787 | ambiguous | -0.114 | Destabilizing | 0.922 | D | 0.527 | neutral | N | 0.484054876 | None | None | N |
| R/M | 0.4861 | ambiguous | 0.4558 | ambiguous | -0.262 | Destabilizing | 0.994 | D | 0.635 | neutral | None | None | None | None | N |
| R/N | 0.7319 | likely_pathogenic | 0.7298 | pathogenic | -0.221 | Destabilizing | 0.956 | D | 0.542 | neutral | None | None | None | None | N |
| R/P | 0.9416 | likely_pathogenic | 0.9493 | pathogenic | -0.337 | Destabilizing | 0.988 | D | 0.679 | prob.neutral | N | 0.484921668 | None | None | N |
| R/Q | 0.1473 | likely_benign | 0.1387 | benign | -0.505 | Destabilizing | 0.447 | N | 0.315 | neutral | N | 0.483188084 | None | None | N |
| R/S | 0.6031 | likely_pathogenic | 0.5929 | pathogenic | -1.01 | Destabilizing | 0.754 | D | 0.57 | neutral | None | None | None | None | N |
| R/T | 0.3689 | ambiguous | 0.3365 | benign | -0.752 | Destabilizing | 0.956 | D | 0.58 | neutral | None | None | None | None | N |
| R/V | 0.5046 | ambiguous | 0.4709 | ambiguous | -0.337 | Destabilizing | 0.956 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/W | 0.2923 | likely_benign | 0.2971 | benign | -0.55 | Destabilizing | 0.998 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/Y | 0.5504 | ambiguous | 0.5371 | ambiguous | -0.227 | Destabilizing | 0.978 | D | 0.68 | prob.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.