Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30676 | 92251;92252;92253 | chr2:178549696;178549695;178549694 | chr2:179414423;179414422;179414421 |
| N2AB | 29035 | 87328;87329;87330 | chr2:178549696;178549695;178549694 | chr2:179414423;179414422;179414421 |
| N2A | 28108 | 84547;84548;84549 | chr2:178549696;178549695;178549694 | chr2:179414423;179414422;179414421 |
| N2B | 21611 | 65056;65057;65058 | chr2:178549696;178549695;178549694 | chr2:179414423;179414422;179414421 |
| Novex-1 | 21736 | 65431;65432;65433 | chr2:178549696;178549695;178549694 | chr2:179414423;179414422;179414421 |
| Novex-2 | 21803 | 65632;65633;65634 | chr2:178549696;178549695;178549694 | chr2:179414423;179414422;179414421 |
| 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/G | rs1237501659  |
-0.755 | 0.014 | N | 0.214 | 0.123 | 0.149567049428 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| A/G | rs1237501659 |
-0.755 | 0.014 | N | 0.214 | 0.123 | 0.149567049428 | gnomAD-4.0.0 | 6.40595E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57268E-06 | 1.3403E-05 | 0 |
| A/T | None | None | 0.698 | N | 0.485 | 0.174 | 0.170165803431 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 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 | 0.4077 | ambiguous | 0.3973 | ambiguous | -0.65 | Destabilizing | 0.998 | D | 0.649 | neutral | None | None | None | None | N |
| A/D | 0.2097 | likely_benign | 0.308 | benign | -1.137 | Destabilizing | 0.942 | D | 0.656 | neutral | N | 0.443677186 | None | None | N |
| A/E | 0.1909 | likely_benign | 0.2695 | benign | -1.113 | Destabilizing | 0.956 | D | 0.607 | neutral | None | None | None | None | N |
| A/F | 0.2578 | likely_benign | 0.3144 | benign | -0.818 | Destabilizing | 0.993 | D | 0.697 | prob.neutral | None | None | None | None | N |
| A/G | 0.1067 | likely_benign | 0.1159 | benign | -1.06 | Destabilizing | 0.014 | N | 0.214 | neutral | N | 0.436751213 | None | None | N |
| A/H | 0.3742 | ambiguous | 0.4203 | ambiguous | -1.145 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| A/I | 0.1894 | likely_benign | 0.2217 | benign | -0.134 | Destabilizing | 0.978 | D | 0.686 | prob.neutral | None | None | None | None | N |
| A/K | 0.3158 | likely_benign | 0.4038 | ambiguous | -1.03 | Destabilizing | 0.956 | D | 0.603 | neutral | None | None | None | None | N |
| A/L | 0.1531 | likely_benign | 0.1629 | benign | -0.134 | Destabilizing | 0.978 | D | 0.573 | neutral | None | None | None | None | N |
| A/M | 0.1639 | likely_benign | 0.1703 | benign | -0.193 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | None | None | None | None | N |
| A/N | 0.1686 | likely_benign | 0.2005 | benign | -0.858 | Destabilizing | 0.956 | D | 0.671 | neutral | None | None | None | None | N |
| A/P | 0.444 | ambiguous | 0.4645 | ambiguous | -0.307 | Destabilizing | 0.971 | D | 0.691 | prob.neutral | N | 0.474028584 | None | None | N |
| A/Q | 0.2433 | likely_benign | 0.2734 | benign | -0.934 | Destabilizing | 0.978 | D | 0.695 | prob.neutral | None | None | None | None | N |
| A/R | 0.3257 | likely_benign | 0.4045 | ambiguous | -0.752 | Destabilizing | 0.978 | D | 0.687 | prob.neutral | None | None | None | None | N |
| A/S | 0.0794 | likely_benign | 0.0895 | benign | -1.189 | Destabilizing | 0.294 | N | 0.241 | neutral | N | 0.440578166 | None | None | N |
| A/T | 0.0728 | likely_benign | 0.082 | benign | -1.06 | Destabilizing | 0.698 | D | 0.485 | neutral | N | 0.409444395 | None | None | N |
| A/V | 0.1038 | likely_benign | 0.1219 | benign | -0.307 | Destabilizing | 0.904 | D | 0.528 | neutral | N | 0.485985168 | None | None | N |
| A/W | 0.6401 | likely_pathogenic | 0.6941 | pathogenic | -1.231 | Destabilizing | 0.998 | D | 0.733 | prob.delet. | None | None | None | None | N |
| A/Y | 0.3596 | ambiguous | 0.4083 | ambiguous | -0.761 | Destabilizing | 0.993 | D | 0.695 | 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.