Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14400 | 43423;43424;43425 | chr2:178632933;178632932;178632931 | chr2:179497660;179497659;179497658 |
| N2AB | 12759 | 38500;38501;38502 | chr2:178632933;178632932;178632931 | chr2:179497660;179497659;179497658 |
| N2A | 11832 | 35719;35720;35721 | chr2:178632933;178632932;178632931 | chr2:179497660;179497659;179497658 |
| N2B | 5335 | 16228;16229;16230 | chr2:178632933;178632932;178632931 | chr2:179497660;179497659;179497658 |
| Novex-1 | 5460 | 16603;16604;16605 | chr2:178632933;178632932;178632931 | chr2:179497660;179497659;179497658 |
| Novex-2 | 5527 | 16804;16805;16806 | chr2:178632933;178632932;178632931 | chr2:179497660;179497659;179497658 |
| 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/H | rs775820574  |
-0.853 | 0.481 | N | 0.636 | 0.182 | 0.170165803431 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| N/H | rs775820574 |
-0.853 | 0.481 | N | 0.636 | 0.182 | 0.170165803431 | gnomAD-4.0.0 | 3.18763E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72367E-06 | 0 | 0 |
| N/K | None | None | None | N | 0.267 | 0.11 | 0.0482279557977 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| N/S | rs772475209 |
-0.308 | None | N | 0.293 | 0.097 | 0.104622674875 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| N/S | rs772475209 |
-0.308 | None | N | 0.293 | 0.097 | 0.104622674875 | gnomAD-4.0.0 | 1.59372E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43707E-05 | 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 | 0.228 | likely_benign | 0.1897 | benign | -0.873 | Destabilizing | 0.08 | N | 0.663 | prob.neutral | None | None | None | None | N |
| N/C | 0.3483 | ambiguous | 0.3476 | ambiguous | 0.024 | Stabilizing | 0.823 | D | 0.769 | deleterious | None | None | None | None | N |
| N/D | 0.1731 | likely_benign | 0.1551 | benign | -0.11 | Destabilizing | 0.061 | N | 0.529 | neutral | N | 0.412689587 | None | None | N |
| N/E | 0.362 | ambiguous | 0.3223 | benign | -0.048 | Destabilizing | 0.08 | N | 0.541 | neutral | None | None | None | None | N |
| N/F | 0.4814 | ambiguous | 0.4294 | ambiguous | -0.794 | Destabilizing | 0.552 | D | 0.79 | deleterious | None | None | None | None | N |
| N/G | 0.3683 | ambiguous | 0.3161 | benign | -1.171 | Destabilizing | 0.08 | N | 0.547 | neutral | None | None | None | None | N |
| N/H | 0.0974 | likely_benign | 0.0999 | benign | -0.884 | Destabilizing | 0.481 | N | 0.636 | neutral | N | 0.431252694 | None | None | N |
| N/I | 0.183 | likely_benign | 0.1602 | benign | -0.134 | Destabilizing | 0.314 | N | 0.787 | deleterious | N | 0.434857819 | None | None | N |
| N/K | 0.1896 | likely_benign | 0.1646 | benign | -0.051 | Destabilizing | None | N | 0.267 | neutral | N | 0.419930466 | None | None | N |
| N/L | 0.192 | likely_benign | 0.1879 | benign | -0.134 | Destabilizing | 0.378 | N | 0.743 | deleterious | None | None | None | None | N |
| N/M | 0.2956 | likely_benign | 0.2697 | benign | 0.283 | Stabilizing | 0.934 | D | 0.742 | deleterious | None | None | None | None | N |
| N/P | 0.5248 | ambiguous | 0.4419 | ambiguous | -0.352 | Destabilizing | 0.378 | N | 0.753 | deleterious | None | None | None | None | N |
| N/Q | 0.2698 | likely_benign | 0.2546 | benign | -0.671 | Destabilizing | 0.233 | N | 0.586 | neutral | None | None | None | None | N |
| N/R | 0.2291 | likely_benign | 0.2298 | benign | -0.013 | Destabilizing | 0.08 | N | 0.592 | neutral | None | None | None | None | N |
| N/S | 0.0847 | likely_benign | 0.0772 | benign | -0.676 | Destabilizing | None | N | 0.293 | neutral | N | 0.432054662 | None | None | N |
| N/T | 0.1118 | likely_benign | 0.1031 | benign | -0.421 | Destabilizing | 0.061 | N | 0.493 | neutral | N | 0.431410336 | None | None | N |
| N/V | 0.178 | likely_benign | 0.1624 | benign | -0.352 | Destabilizing | 0.378 | N | 0.731 | deleterious | None | None | None | None | N |
| N/W | 0.761 | likely_pathogenic | 0.7363 | pathogenic | -0.534 | Destabilizing | 0.934 | D | 0.686 | prob.delet. | None | None | None | None | N |
| N/Y | 0.1575 | likely_benign | 0.1582 | benign | -0.335 | Destabilizing | 0.481 | N | 0.768 | deleterious | N | 0.475339264 | 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.