Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26352 | 79279;79280;79281 | chr2:178567078;178567077;178567076 | chr2:179431805;179431804;179431803 |
| N2AB | 24711 | 74356;74357;74358 | chr2:178567078;178567077;178567076 | chr2:179431805;179431804;179431803 |
| N2A | 23784 | 71575;71576;71577 | chr2:178567078;178567077;178567076 | chr2:179431805;179431804;179431803 |
| N2B | 17287 | 52084;52085;52086 | chr2:178567078;178567077;178567076 | chr2:179431805;179431804;179431803 |
| Novex-1 | 17412 | 52459;52460;52461 | chr2:178567078;178567077;178567076 | chr2:179431805;179431804;179431803 |
| Novex-2 | 17479 | 52660;52661;52662 | chr2:178567078;178567077;178567076 | chr2:179431805;179431804;179431803 |
| 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 | None | None | 0.988 | N | 0.661 | 0.203 | 0.532890898078 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31252E-06 | 0 | 0 |
| L/S | rs753271373  |
-1.115 | 0.994 | N | 0.689 | 0.549 | 0.750802705713 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| L/S | rs753271373 |
-1.115 | 0.994 | N | 0.689 | 0.549 | 0.750802705713 | gnomAD-4.0.0 | 3.18344E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.7187E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9218 | likely_pathogenic | 0.9071 | pathogenic | -1.203 | Destabilizing | 0.968 | D | 0.563 | neutral | None | None | None | None | N |
| L/C | 0.9731 | likely_pathogenic | 0.969 | pathogenic | -0.791 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | N |
| L/D | 0.998 | likely_pathogenic | 0.9975 | pathogenic | -0.293 | Destabilizing | 0.998 | D | 0.707 | prob.neutral | None | None | None | None | N |
| L/E | 0.9859 | likely_pathogenic | 0.9815 | pathogenic | -0.307 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| L/F | 0.8568 | likely_pathogenic | 0.7984 | pathogenic | -0.806 | Destabilizing | 0.988 | D | 0.661 | neutral | N | 0.492892498 | None | None | N |
| L/G | 0.9864 | likely_pathogenic | 0.9839 | pathogenic | -1.486 | Destabilizing | 0.995 | D | 0.698 | prob.neutral | None | None | None | None | N |
| L/H | 0.957 | likely_pathogenic | 0.9517 | pathogenic | -0.55 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| L/I | 0.3311 | likely_benign | 0.328 | benign | -0.525 | Destabilizing | 0.142 | N | 0.254 | neutral | N | 0.412372844 | None | None | N |
| L/K | 0.9449 | likely_pathogenic | 0.9438 | pathogenic | -0.64 | Destabilizing | 0.995 | D | 0.686 | prob.neutral | None | None | None | None | N |
| L/M | 0.4811 | ambiguous | 0.4388 | ambiguous | -0.508 | Destabilizing | 0.991 | D | 0.654 | neutral | None | None | None | None | N |
| L/N | 0.9806 | likely_pathogenic | 0.9804 | pathogenic | -0.485 | Destabilizing | 0.998 | D | 0.703 | prob.neutral | None | None | None | None | N |
| L/P | 0.9805 | likely_pathogenic | 0.9778 | pathogenic | -0.718 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | N |
| L/Q | 0.9184 | likely_pathogenic | 0.9003 | pathogenic | -0.637 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| L/R | 0.8961 | likely_pathogenic | 0.8864 | pathogenic | -0.083 | Destabilizing | 0.998 | D | 0.709 | prob.delet. | None | None | None | None | N |
| L/S | 0.9792 | likely_pathogenic | 0.9756 | pathogenic | -1.119 | Destabilizing | 0.994 | D | 0.689 | prob.neutral | N | 0.462414875 | None | None | N |
| L/T | 0.9114 | likely_pathogenic | 0.9121 | pathogenic | -1.007 | Destabilizing | 0.991 | D | 0.643 | neutral | None | None | None | None | N |
| L/V | 0.5491 | ambiguous | 0.5292 | ambiguous | -0.718 | Destabilizing | 0.618 | D | 0.412 | neutral | N | 0.465551181 | None | None | N |
| L/W | 0.9331 | likely_pathogenic | 0.9158 | pathogenic | -0.822 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| L/Y | 0.9705 | likely_pathogenic | 0.9584 | pathogenic | -0.593 | Destabilizing | 0.995 | D | 0.69 | 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.