Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19762 | 59509;59510;59511 | chr2:178592835;178592834;178592833 | chr2:179457562;179457561;179457560 |
| N2AB | 18121 | 54586;54587;54588 | chr2:178592835;178592834;178592833 | chr2:179457562;179457561;179457560 |
| N2A | 17194 | 51805;51806;51807 | chr2:178592835;178592834;178592833 | chr2:179457562;179457561;179457560 |
| N2B | 10697 | 32314;32315;32316 | chr2:178592835;178592834;178592833 | chr2:179457562;179457561;179457560 |
| Novex-1 | 10822 | 32689;32690;32691 | chr2:178592835;178592834;178592833 | chr2:179457562;179457561;179457560 |
| Novex-2 | 10889 | 32890;32891;32892 | chr2:178592835;178592834;178592833 | chr2:179457562;179457561;179457560 |
| 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/E | rs1311886410  |
-0.102 | 0.001 | N | 0.291 | 0.069 | 0.213573922156 | 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/E | rs1311886410 |
-0.102 | 0.001 | N | 0.291 | 0.069 | 0.213573922156 | 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 |
| A/E | rs1311886410 |
-0.102 | 0.001 | N | 0.291 | 0.069 | 0.213573922156 | gnomAD-4.0.0 | 1.79746E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.4584E-05 | 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 | 0.5165 | ambiguous | 0.5308 | ambiguous | -0.888 | Destabilizing | 0.909 | D | 0.393 | neutral | None | None | None | None | I |
| A/D | 0.179 | likely_benign | 0.1614 | benign | -0.242 | Destabilizing | 0.157 | N | 0.539 | neutral | None | None | None | None | I |
| A/E | 0.0888 | likely_benign | 0.062 | benign | -0.386 | Destabilizing | 0.001 | N | 0.291 | neutral | N | 0.480635277 | None | None | I |
| A/F | 0.3969 | ambiguous | 0.4565 | ambiguous | -0.774 | Destabilizing | 0.567 | D | 0.62 | neutral | None | None | None | None | I |
| A/G | 0.1528 | likely_benign | 0.1441 | benign | -0.232 | Destabilizing | 0.22 | N | 0.349 | neutral | N | 0.465031547 | None | None | I |
| A/H | 0.3803 | ambiguous | 0.3653 | ambiguous | -0.173 | Destabilizing | 0.909 | D | 0.607 | neutral | None | None | None | None | I |
| A/I | 0.1805 | likely_benign | 0.207 | benign | -0.306 | Destabilizing | 0.184 | N | 0.421 | neutral | None | None | None | None | I |
| A/K | 0.2077 | likely_benign | 0.1754 | benign | -0.491 | Destabilizing | 0.003 | N | 0.343 | neutral | None | None | None | None | I |
| A/L | 0.1527 | likely_benign | 0.1776 | benign | -0.306 | Destabilizing | 0.157 | N | 0.452 | neutral | None | None | None | None | I |
| A/M | 0.185 | likely_benign | 0.2048 | benign | -0.452 | Destabilizing | 0.832 | D | 0.457 | neutral | None | None | None | None | I |
| A/N | 0.2399 | likely_benign | 0.237 | benign | -0.283 | Destabilizing | 0.567 | D | 0.603 | neutral | None | None | None | None | I |
| A/P | 0.4369 | ambiguous | 0.3937 | ambiguous | -0.241 | Destabilizing | 0.667 | D | 0.463 | neutral | N | 0.46977585 | None | None | I |
| A/Q | 0.17 | likely_benign | 0.1334 | benign | -0.52 | Destabilizing | 0.396 | N | 0.461 | neutral | None | None | None | None | I |
| A/R | 0.2653 | likely_benign | 0.2288 | benign | -0.075 | Destabilizing | 0.396 | N | 0.433 | neutral | None | None | None | None | I |
| A/S | 0.1109 | likely_benign | 0.1201 | benign | -0.521 | Destabilizing | 0.124 | N | 0.389 | neutral | N | 0.491486988 | None | None | I |
| A/T | 0.0938 | likely_benign | 0.0978 | benign | -0.578 | Destabilizing | 0.22 | N | 0.373 | neutral | N | 0.468962475 | None | None | I |
| A/V | 0.1107 | likely_benign | 0.1212 | benign | -0.241 | Destabilizing | 0.002 | N | 0.289 | neutral | N | 0.472129253 | None | None | I |
| A/W | 0.7465 | likely_pathogenic | 0.7466 | pathogenic | -0.889 | Destabilizing | 0.968 | D | 0.703 | prob.neutral | None | None | None | None | I |
| A/Y | 0.4163 | ambiguous | 0.4376 | ambiguous | -0.553 | Destabilizing | 0.726 | D | 0.618 | 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.