Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22066 | 66421;66422;66423 | chr2:178582173;178582172;178582171 | chr2:179446900;179446899;179446898 |
| N2AB | 20425 | 61498;61499;61500 | chr2:178582173;178582172;178582171 | chr2:179446900;179446899;179446898 |
| N2A | 19498 | 58717;58718;58719 | chr2:178582173;178582172;178582171 | chr2:179446900;179446899;179446898 |
| N2B | 13001 | 39226;39227;39228 | chr2:178582173;178582172;178582171 | chr2:179446900;179446899;179446898 |
| Novex-1 | 13126 | 39601;39602;39603 | chr2:178582173;178582172;178582171 | chr2:179446900;179446899;179446898 |
| Novex-2 | 13193 | 39802;39803;39804 | chr2:178582173;178582172;178582171 | chr2:179446900;179446899;179446898 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs1394300458  |
0.339 | 0.958 | N | 0.477 | 0.352 | 0.180583059064 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| N/D | rs1394300458 |
0.339 | 0.958 | N | 0.477 | 0.352 | 0.180583059064 | gnomAD-4.0.0 | 8.21548E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89661E-06 | 0 | 1.65744E-05 |
| N/S | rs1400000859 |
0.15 | 0.958 | N | 0.407 | 0.312 | 0.151104730317 | gnomAD-2.1.1 | 7.19E-06 | None | None | None | None | N | None | 4.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.89E-06 | 0 |
| N/S | rs1400000859 |
0.15 | 0.958 | N | 0.407 | 0.312 | 0.151104730317 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/S | rs1400000859 |
0.15 | 0.958 | N | 0.407 | 0.312 | 0.151104730317 | gnomAD-4.0.0 | 1.97291E-05 | None | None | None | None | N | None | 4.82532E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47089E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.331 | likely_benign | 0.4061 | ambiguous | -0.401 | Destabilizing | 0.938 | D | 0.557 | neutral | None | None | None | None | N |
| N/C | 0.3802 | ambiguous | 0.4558 | ambiguous | 0.379 | Stabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| N/D | 0.3734 | ambiguous | 0.3398 | benign | -0.007 | Destabilizing | 0.958 | D | 0.477 | neutral | N | 0.454160751 | None | None | N |
| N/E | 0.7473 | likely_pathogenic | 0.725 | pathogenic | -0.031 | Destabilizing | 0.938 | D | 0.5 | neutral | None | None | None | None | N |
| N/F | 0.7559 | likely_pathogenic | 0.8234 | pathogenic | -0.696 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| N/G | 0.3771 | ambiguous | 0.4489 | ambiguous | -0.599 | Destabilizing | 0.968 | D | 0.435 | neutral | None | None | None | None | N |
| N/H | 0.1887 | likely_benign | 0.2105 | benign | -0.639 | Destabilizing | 0.994 | D | 0.624 | neutral | N | 0.468801572 | None | None | N |
| N/I | 0.5875 | likely_pathogenic | 0.6736 | pathogenic | 0.041 | Stabilizing | 0.994 | D | 0.744 | deleterious | N | 0.489058647 | None | None | N |
| N/K | 0.7716 | likely_pathogenic | 0.7567 | pathogenic | 0.012 | Stabilizing | 0.067 | N | 0.288 | neutral | N | 0.456433052 | None | None | N |
| N/L | 0.4191 | ambiguous | 0.5013 | ambiguous | 0.041 | Stabilizing | 0.991 | D | 0.672 | neutral | None | None | None | None | N |
| N/M | 0.5492 | ambiguous | 0.6339 | pathogenic | 0.437 | Stabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| N/P | 0.9593 | likely_pathogenic | 0.956 | pathogenic | -0.078 | Destabilizing | 0.995 | D | 0.692 | prob.neutral | None | None | None | None | N |
| N/Q | 0.5881 | likely_pathogenic | 0.6143 | pathogenic | -0.44 | Destabilizing | 0.991 | D | 0.659 | neutral | None | None | None | None | N |
| N/R | 0.7433 | likely_pathogenic | 0.7141 | pathogenic | 0.055 | Stabilizing | 0.982 | D | 0.599 | neutral | None | None | None | None | N |
| N/S | 0.1054 | likely_benign | 0.1244 | benign | -0.213 | Destabilizing | 0.958 | D | 0.407 | neutral | N | 0.44938965 | None | None | N |
| N/T | 0.2694 | likely_benign | 0.3041 | benign | -0.088 | Destabilizing | 0.958 | D | 0.536 | neutral | N | 0.499626469 | None | None | N |
| N/V | 0.4566 | ambiguous | 0.5428 | ambiguous | -0.078 | Destabilizing | 0.991 | D | 0.737 | prob.delet. | None | None | None | None | N |
| N/W | 0.9287 | likely_pathogenic | 0.9408 | pathogenic | -0.658 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| N/Y | 0.3608 | ambiguous | 0.4138 | ambiguous | -0.408 | Destabilizing | 0.998 | D | 0.69 | prob.neutral | N | 0.474562016 | 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.