Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33694 | 101305;101306;101307 | chr2:178535535;178535534;178535533 | chr2:179400262;179400261;179400260 |
| N2AB | 32053 | 96382;96383;96384 | chr2:178535535;178535534;178535533 | chr2:179400262;179400261;179400260 |
| N2A | 31126 | 93601;93602;93603 | chr2:178535535;178535534;178535533 | chr2:179400262;179400261;179400260 |
| N2B | 24629 | 74110;74111;74112 | chr2:178535535;178535534;178535533 | chr2:179400262;179400261;179400260 |
| Novex-1 | 24754 | 74485;74486;74487 | chr2:178535535;178535534;178535533 | chr2:179400262;179400261;179400260 |
| Novex-2 | 24821 | 74686;74687;74688 | chr2:178535535;178535534;178535533 | chr2:179400262;179400261;179400260 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs747732590  |
-0.321 | 0.048 | N | 0.202 | 0.146 | 0.264547087235 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| R/K | rs747732590 |
-0.321 | 0.048 | N | 0.202 | 0.146 | 0.264547087235 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs747732590 |
-0.321 | 0.048 | N | 0.202 | 0.146 | 0.264547087235 | gnomAD-4.0.0 | 5.12394E-06 | None | None | None | None | N | None | 1.69125E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78556E-06 | 0 | 2.84398E-05 |
| R/T | rs747732590 |
None | 0.993 | N | 0.715 | 0.288 | 0.568072681961 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs747732590 |
None | 0.993 | N | 0.715 | 0.288 | 0.568072681961 | gnomAD-4.0.0 | 6.57065E-06 | None | None | None | None | N | None | 0 | 6.54707E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3713 | ambiguous | 0.3329 | benign | -0.51 | Destabilizing | 0.99 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/C | 0.1772 | likely_benign | 0.1692 | benign | -0.448 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| R/D | 0.7622 | likely_pathogenic | 0.7257 | pathogenic | 0.058 | Stabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/E | 0.4161 | ambiguous | 0.3643 | ambiguous | 0.186 | Stabilizing | 0.967 | D | 0.618 | neutral | None | None | None | None | N |
| R/F | 0.617 | likely_pathogenic | 0.5676 | pathogenic | -0.335 | Destabilizing | 0.999 | D | 0.774 | deleterious | None | None | None | None | N |
| R/G | 0.2934 | likely_benign | 0.2443 | benign | -0.827 | Destabilizing | 0.993 | D | 0.707 | prob.neutral | N | 0.467514051 | None | None | N |
| R/H | 0.1289 | likely_benign | 0.1205 | benign | -1.219 | Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | N |
| R/I | 0.3074 | likely_benign | 0.2748 | benign | 0.334 | Stabilizing | 0.998 | D | 0.784 | deleterious | N | 0.471688407 | None | None | N |
| R/K | 0.0972 | likely_benign | 0.1 | benign | -0.532 | Destabilizing | 0.048 | N | 0.202 | neutral | N | 0.47890448 | None | None | N |
| R/L | 0.2775 | likely_benign | 0.2519 | benign | 0.334 | Stabilizing | 0.988 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/M | 0.3275 | likely_benign | 0.3123 | benign | -0.079 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/N | 0.6363 | likely_pathogenic | 0.5988 | pathogenic | -0.07 | Destabilizing | 0.999 | D | 0.634 | neutral | None | None | None | None | N |
| R/P | 0.8909 | likely_pathogenic | 0.8197 | pathogenic | 0.075 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/Q | 0.1071 | likely_benign | 0.1025 | benign | -0.178 | Destabilizing | 0.996 | D | 0.656 | neutral | None | None | None | None | N |
| R/S | 0.4885 | ambiguous | 0.4313 | ambiguous | -0.737 | Destabilizing | 0.987 | D | 0.701 | prob.neutral | N | 0.466012541 | None | None | N |
| R/T | 0.2559 | likely_benign | 0.2218 | benign | -0.425 | Destabilizing | 0.993 | D | 0.715 | prob.delet. | N | 0.474997383 | None | None | N |
| R/V | 0.3401 | ambiguous | 0.3147 | benign | 0.075 | Stabilizing | 0.995 | D | 0.759 | deleterious | None | None | None | None | N |
| R/W | 0.2874 | likely_benign | 0.2425 | benign | -0.067 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| R/Y | 0.4842 | ambiguous | 0.4463 | ambiguous | 0.245 | Stabilizing | 0.999 | D | 0.788 | deleterious | 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.