Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27549 | 82870;82871;82872 | chr2:178563487;178563486;178563485 | chr2:179428214;179428213;179428212 |
| N2AB | 25908 | 77947;77948;77949 | chr2:178563487;178563486;178563485 | chr2:179428214;179428213;179428212 |
| N2A | 24981 | 75166;75167;75168 | chr2:178563487;178563486;178563485 | chr2:179428214;179428213;179428212 |
| N2B | 18484 | 55675;55676;55677 | chr2:178563487;178563486;178563485 | chr2:179428214;179428213;179428212 |
| Novex-1 | 18609 | 56050;56051;56052 | chr2:178563487;178563486;178563485 | chr2:179428214;179428213;179428212 |
| Novex-2 | 18676 | 56251;56252;56253 | chr2:178563487;178563486;178563485 | chr2:179428214;179428213;179428212 |
| 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 | rs749950083  |
-0.395 | 0.994 | N | 0.662 | 0.275 | 0.512883945787 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| A/V | rs749950083 |
0.072 | 0.919 | N | 0.467 | 0.238 | 0.454238212503 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 1.17924E-03 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs749950083 |
0.072 | 0.919 | N | 0.467 | 0.238 | 0.454238212503 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs749950083 |
0.072 | 0.919 | N | 0.467 | 0.238 | 0.454238212503 | gnomAD-4.0.0 | 3.84376E-06 | None | None | None | None | I | None | 0 | 5.08561E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4559 | ambiguous | 0.5091 | ambiguous | -0.722 | Destabilizing | 1.0 | D | 0.636 | neutral | None | None | None | None | I |
| A/D | 0.3626 | ambiguous | 0.4096 | ambiguous | -0.63 | Destabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | I |
| A/E | 0.2387 | likely_benign | 0.2767 | benign | -0.799 | Destabilizing | 0.994 | D | 0.662 | neutral | N | 0.494372578 | None | None | I |
| A/F | 0.3465 | ambiguous | 0.3958 | ambiguous | -0.926 | Destabilizing | 0.991 | D | 0.688 | prob.neutral | None | None | None | None | I |
| A/G | 0.1793 | likely_benign | 0.1964 | benign | -0.233 | Destabilizing | 0.979 | D | 0.509 | neutral | N | 0.482477465 | None | None | I |
| A/H | 0.4553 | ambiguous | 0.5158 | ambiguous | -0.241 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| A/I | 0.1687 | likely_benign | 0.2133 | benign | -0.357 | Destabilizing | 0.982 | D | 0.61 | neutral | None | None | None | None | I |
| A/K | 0.2843 | likely_benign | 0.3474 | ambiguous | -0.549 | Destabilizing | 0.995 | D | 0.674 | neutral | None | None | None | None | I |
| A/L | 0.1461 | likely_benign | 0.1579 | benign | -0.357 | Destabilizing | 0.086 | N | 0.447 | neutral | None | None | None | None | I |
| A/M | 0.1734 | likely_benign | 0.2038 | benign | -0.358 | Destabilizing | 0.998 | D | 0.645 | neutral | None | None | None | None | I |
| A/N | 0.282 | likely_benign | 0.3206 | benign | -0.225 | Destabilizing | 0.998 | D | 0.693 | prob.neutral | None | None | None | None | I |
| A/P | 0.3413 | ambiguous | 0.3876 | ambiguous | -0.278 | Destabilizing | 0.998 | D | 0.654 | neutral | N | 0.478827977 | None | None | I |
| A/Q | 0.2878 | likely_benign | 0.3312 | benign | -0.554 | Destabilizing | 0.998 | D | 0.67 | neutral | None | None | None | None | I |
| A/R | 0.2739 | likely_benign | 0.3334 | benign | -0.033 | Destabilizing | 0.995 | D | 0.653 | neutral | None | None | None | None | I |
| A/S | 0.1235 | likely_benign | 0.1256 | benign | -0.383 | Destabilizing | 0.979 | D | 0.499 | neutral | N | 0.504416213 | None | None | I |
| A/T | 0.0921 | likely_benign | 0.1064 | benign | -0.481 | Destabilizing | 0.988 | D | 0.632 | neutral | N | 0.473406246 | None | None | I |
| A/V | 0.0946 | likely_benign | 0.1177 | benign | -0.278 | Destabilizing | 0.919 | D | 0.467 | neutral | N | 0.474268847 | None | None | I |
| A/W | 0.7175 | likely_pathogenic | 0.7718 | pathogenic | -1.035 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | I |
| A/Y | 0.4881 | ambiguous | 0.5366 | ambiguous | -0.69 | Destabilizing | 0.995 | D | 0.695 | prob.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.