Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31454 | 94585;94586;94587 | chr2:178547165;178547164;178547163 | chr2:179411892;179411891;179411890 |
| N2AB | 29813 | 89662;89663;89664 | chr2:178547165;178547164;178547163 | chr2:179411892;179411891;179411890 |
| N2A | 28886 | 86881;86882;86883 | chr2:178547165;178547164;178547163 | chr2:179411892;179411891;179411890 |
| N2B | 22389 | 67390;67391;67392 | chr2:178547165;178547164;178547163 | chr2:179411892;179411891;179411890 |
| Novex-1 | 22514 | 67765;67766;67767 | chr2:178547165;178547164;178547163 | chr2:179411892;179411891;179411890 |
| Novex-2 | 22581 | 67966;67967;67968 | chr2:178547165;178547164;178547163 | chr2:179411892;179411891;179411890 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs758766295  |
-0.519 | 1.0 | N | 0.577 | 0.31 | 0.628150982837 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/F | rs758766295 |
-0.519 | 1.0 | N | 0.577 | 0.31 | 0.628150982837 | gnomAD-4.0.0 | 5.47357E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 9.2745E-05 | 0 |
| L/I | rs758766295 |
-0.13 | 0.999 | N | 0.471 | 0.253 | 0.559044820595 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| L/I | rs758766295 |
-0.13 | 0.999 | N | 0.471 | 0.253 | 0.559044820595 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 2.88184E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/I | rs758766295 |
-0.13 | 0.999 | N | 0.471 | 0.253 | 0.559044820595 | gnomAD-4.0.0 | 2.4788E-06 | None | None | None | None | I | None | 0 | 0 | None | 1.01365E-04 | 0 | None | 0 | 0 | 8.47606E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9275 | likely_pathogenic | 0.9003 | pathogenic | -0.768 | Destabilizing | 0.999 | D | 0.565 | neutral | None | None | None | None | I |
| L/C | 0.9494 | likely_pathogenic | 0.9273 | pathogenic | -0.662 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | I |
| L/D | 0.9967 | likely_pathogenic | 0.9952 | pathogenic | -0.277 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| L/E | 0.978 | likely_pathogenic | 0.9712 | pathogenic | -0.328 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| L/F | 0.7551 | likely_pathogenic | 0.7031 | pathogenic | -0.607 | Destabilizing | 1.0 | D | 0.577 | neutral | N | 0.512843696 | None | None | I |
| L/G | 0.9812 | likely_pathogenic | 0.9754 | pathogenic | -0.961 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| L/H | 0.9024 | likely_pathogenic | 0.8737 | pathogenic | -0.083 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.476768252 | None | None | I |
| L/I | 0.3896 | ambiguous | 0.3488 | ambiguous | -0.355 | Destabilizing | 0.999 | D | 0.471 | neutral | N | 0.499471753 | None | None | I |
| L/K | 0.9282 | likely_pathogenic | 0.91 | pathogenic | -0.447 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| L/M | 0.4051 | ambiguous | 0.366 | ambiguous | -0.549 | Destabilizing | 1.0 | D | 0.538 | neutral | None | None | None | None | I |
| L/N | 0.9616 | likely_pathogenic | 0.9475 | pathogenic | -0.324 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| L/P | 0.9911 | likely_pathogenic | 0.9875 | pathogenic | -0.461 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | N | 0.493564501 | None | None | I |
| L/Q | 0.8394 | likely_pathogenic | 0.804 | pathogenic | -0.489 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| L/R | 0.821 | likely_pathogenic | 0.8096 | pathogenic | 0.09 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.426243431 | None | None | I |
| L/S | 0.9642 | likely_pathogenic | 0.9468 | pathogenic | -0.788 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| L/T | 0.9216 | likely_pathogenic | 0.8876 | pathogenic | -0.727 | Destabilizing | 1.0 | D | 0.608 | neutral | None | None | None | None | I |
| L/V | 0.525 | ambiguous | 0.4594 | ambiguous | -0.461 | Destabilizing | 0.999 | D | 0.527 | neutral | N | 0.487542606 | None | None | I |
| L/W | 0.91 | likely_pathogenic | 0.8855 | pathogenic | -0.632 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | I |
| L/Y | 0.9201 | likely_pathogenic | 0.8982 | pathogenic | -0.401 | Destabilizing | 1.0 | D | 0.624 | 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.