Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1155 | 3688;3689;3690 | chr2:178781181;178781180;178781179 | chr2:179645908;179645907;179645906 |
| N2AB | 1155 | 3688;3689;3690 | chr2:178781181;178781180;178781179 | chr2:179645908;179645907;179645906 |
| N2A | 1155 | 3688;3689;3690 | chr2:178781181;178781180;178781179 | chr2:179645908;179645907;179645906 |
| N2B | 1109 | 3550;3551;3552 | chr2:178781181;178781180;178781179 | chr2:179645908;179645907;179645906 |
| Novex-1 | 1109 | 3550;3551;3552 | chr2:178781181;178781180;178781179 | chr2:179645908;179645907;179645906 |
| Novex-2 | 1109 | 3550;3551;3552 | chr2:178781181;178781180;178781179 | chr2:179645908;179645907;179645906 |
| Novex-3 | 1155 | 3688;3689;3690 | chr2:178781181;178781180;178781179 | chr2:179645908;179645907;179645906 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs755080553  |
-1.633 | 0.4 | N | 0.458 | 0.191 | 0.266843984389 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| T/A | rs755080553 |
-1.633 | 0.4 | N | 0.458 | 0.191 | 0.266843984389 | gnomAD-4.0.0 | 2.05235E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69799E-06 | 0 | 0 |
| T/I | rs1385838473 |
None | 0.997 | N | 0.651 | 0.527 | 0.474248596982 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/I | rs1385838473 |
None | 0.997 | N | 0.651 | 0.527 | 0.474248596982 | gnomAD-4.0.0 | 9.29403E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10172E-05 | 0 | 3.20082E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1839 | likely_benign | 0.1785 | benign | -1.439 | Destabilizing | 0.4 | N | 0.458 | neutral | N | 0.494484972 | None | None | I |
| T/C | 0.7183 | likely_pathogenic | 0.6943 | pathogenic | -1.122 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| T/D | 0.8357 | likely_pathogenic | 0.8117 | pathogenic | -1.36 | Destabilizing | 0.996 | D | 0.644 | neutral | None | None | None | None | I |
| T/E | 0.6295 | likely_pathogenic | 0.6027 | pathogenic | -1.176 | Destabilizing | 0.985 | D | 0.615 | neutral | None | None | None | None | I |
| T/F | 0.6163 | likely_pathogenic | 0.5923 | pathogenic | -1.254 | Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | I |
| T/G | 0.6191 | likely_pathogenic | 0.628 | pathogenic | -1.814 | Destabilizing | 0.985 | D | 0.627 | neutral | None | None | None | None | I |
| T/H | 0.5304 | ambiguous | 0.5118 | ambiguous | -1.808 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| T/I | 0.3823 | ambiguous | 0.3498 | ambiguous | -0.456 | Destabilizing | 0.997 | D | 0.651 | neutral | N | 0.45513876 | None | None | I |
| T/K | 0.5669 | likely_pathogenic | 0.5356 | ambiguous | -0.43 | Destabilizing | 0.985 | D | 0.618 | neutral | None | None | None | None | I |
| T/L | 0.2727 | likely_benign | 0.262 | benign | -0.456 | Destabilizing | 0.985 | D | 0.592 | neutral | None | None | None | None | I |
| T/M | 0.1614 | likely_benign | 0.1535 | benign | -0.476 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | I |
| T/N | 0.3542 | ambiguous | 0.326 | benign | -1.025 | Destabilizing | 0.994 | D | 0.592 | neutral | D | 0.544299417 | None | None | I |
| T/P | 0.9642 | likely_pathogenic | 0.963 | pathogenic | -0.755 | Destabilizing | 0.997 | D | 0.657 | neutral | D | 0.636802915 | None | None | I |
| T/Q | 0.4355 | ambiguous | 0.4283 | ambiguous | -0.924 | Destabilizing | 0.998 | D | 0.693 | prob.neutral | None | None | None | None | I |
| T/R | 0.4587 | ambiguous | 0.4384 | ambiguous | -0.535 | Destabilizing | 0.998 | D | 0.676 | prob.neutral | None | None | None | None | I |
| T/S | 0.1914 | likely_benign | 0.1898 | benign | -1.35 | Destabilizing | 0.659 | D | 0.399 | neutral | N | 0.460064631 | None | None | I |
| T/V | 0.2627 | likely_benign | 0.2472 | benign | -0.755 | Destabilizing | 0.985 | D | 0.569 | neutral | None | None | None | None | I |
| T/W | 0.9029 | likely_pathogenic | 0.9058 | pathogenic | -1.256 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| T/Y | 0.6928 | likely_pathogenic | 0.6745 | pathogenic | -0.91 | Destabilizing | 0.999 | D | 0.751 | deleterious | 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.