Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17476 | 52651;52652;52653 | chr2:178608457;178608456;178608455 | chr2:179473184;179473183;179473182 |
| N2AB | 15835 | 47728;47729;47730 | chr2:178608457;178608456;178608455 | chr2:179473184;179473183;179473182 |
| N2A | 14908 | 44947;44948;44949 | chr2:178608457;178608456;178608455 | chr2:179473184;179473183;179473182 |
| N2B | 8411 | 25456;25457;25458 | chr2:178608457;178608456;178608455 | chr2:179473184;179473183;179473182 |
| Novex-1 | 8536 | 25831;25832;25833 | chr2:178608457;178608456;178608455 | chr2:179473184;179473183;179473182 |
| Novex-2 | 8603 | 26032;26033;26034 | chr2:178608457;178608456;178608455 | chr2:179473184;179473183;179473182 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs766412743  |
0.423 | 0.999 | N | 0.61 | 0.212 | 0.275215494804 | gnomAD-2.1.1 | 8.65E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.91E-05 | 0 |
| K/E | rs766412743 |
0.423 | 0.999 | N | 0.61 | 0.212 | 0.275215494804 | gnomAD-4.0.0 | 4.87377E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.72768E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.4316 | ambiguous | 0.4194 | ambiguous | -0.313 | Destabilizing | 0.999 | D | 0.666 | neutral | None | None | None | None | N |
| K/C | 0.7231 | likely_pathogenic | 0.7203 | pathogenic | -0.241 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| K/D | 0.8296 | likely_pathogenic | 0.8289 | pathogenic | 0.02 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| K/E | 0.3277 | likely_benign | 0.3253 | benign | 0.08 | Stabilizing | 0.999 | D | 0.61 | neutral | N | 0.49960504 | None | None | N |
| K/F | 0.8561 | likely_pathogenic | 0.8432 | pathogenic | -0.183 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| K/G | 0.7364 | likely_pathogenic | 0.7097 | pathogenic | -0.627 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| K/H | 0.5131 | ambiguous | 0.5039 | ambiguous | -1.057 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| K/I | 0.3382 | likely_benign | 0.3592 | ambiguous | 0.471 | Stabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| K/L | 0.4519 | ambiguous | 0.4378 | ambiguous | 0.471 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| K/M | 0.2474 | likely_benign | 0.2507 | benign | 0.398 | Stabilizing | 1.0 | D | 0.648 | neutral | N | 0.466444487 | None | None | N |
| K/N | 0.6174 | likely_pathogenic | 0.6279 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.470970069 | None | None | N |
| K/P | 0.5195 | ambiguous | 0.5461 | ambiguous | 0.24 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| K/Q | 0.1971 | likely_benign | 0.1887 | benign | -0.219 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.484790303 | None | None | N |
| K/R | 0.1125 | likely_benign | 0.1098 | benign | -0.459 | Destabilizing | 0.999 | D | 0.577 | neutral | N | 0.456680982 | None | None | N |
| K/S | 0.5801 | likely_pathogenic | 0.5707 | pathogenic | -0.667 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| K/T | 0.2264 | likely_benign | 0.2213 | benign | -0.424 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.436191066 | None | None | N |
| K/V | 0.3311 | likely_benign | 0.3339 | benign | 0.24 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| K/W | 0.902 | likely_pathogenic | 0.8993 | pathogenic | -0.095 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| K/Y | 0.7263 | likely_pathogenic | 0.7233 | pathogenic | 0.2 | Stabilizing | 1.0 | D | 0.683 | 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.