Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18219 | 54880;54881;54882 | chr2:178604032;178604031;178604030 | chr2:179468759;179468758;179468757 |
| N2AB | 16578 | 49957;49958;49959 | chr2:178604032;178604031;178604030 | chr2:179468759;179468758;179468757 |
| N2A | 15651 | 47176;47177;47178 | chr2:178604032;178604031;178604030 | chr2:179468759;179468758;179468757 |
| N2B | 9154 | 27685;27686;27687 | chr2:178604032;178604031;178604030 | chr2:179468759;179468758;179468757 |
| Novex-1 | 9279 | 28060;28061;28062 | chr2:178604032;178604031;178604030 | chr2:179468759;179468758;179468757 |
| Novex-2 | 9346 | 28261;28262;28263 | chr2:178604032;178604031;178604030 | chr2:179468759;179468758;179468757 |
| 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/V | rs546735795  |
0.025 | 0.704 | N | 0.33 | 0.297 | 0.435479573448 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs546735795 |
0.025 | 0.704 | N | 0.33 | 0.297 | 0.435479573448 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs546735795 |
0.025 | 0.704 | N | 0.33 | 0.297 | 0.435479573448 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/V | rs546735795 |
0.025 | 0.704 | N | 0.33 | 0.297 | 0.435479573448 | gnomAD-4.0.0 | 6.57825E-06 | None | None | None | None | I | None | 2.40906E-05 | 0 | 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 | 0.6143 | likely_pathogenic | 0.6532 | pathogenic | -0.742 | Destabilizing | 0.999 | D | 0.396 | neutral | None | None | None | None | I |
| A/D | 0.717 | likely_pathogenic | 0.6255 | pathogenic | -0.507 | Destabilizing | 0.991 | D | 0.469 | neutral | None | None | None | None | I |
| A/E | 0.6065 | likely_pathogenic | 0.5195 | ambiguous | -0.57 | Destabilizing | 0.988 | D | 0.392 | neutral | N | 0.467197125 | None | None | I |
| A/F | 0.4713 | ambiguous | 0.4088 | ambiguous | -0.726 | Destabilizing | 0.982 | D | 0.489 | neutral | None | None | None | None | I |
| A/G | 0.2447 | likely_benign | 0.2108 | benign | -0.582 | Destabilizing | 0.959 | D | 0.326 | neutral | N | 0.443570903 | None | None | I |
| A/H | 0.6729 | likely_pathogenic | 0.6493 | pathogenic | -0.399 | Destabilizing | 0.999 | D | 0.494 | neutral | None | None | None | None | I |
| A/I | 0.3495 | ambiguous | 0.2955 | benign | -0.221 | Destabilizing | 0.17 | N | 0.26 | neutral | None | None | None | None | I |
| A/K | 0.7656 | likely_pathogenic | 0.7287 | pathogenic | -0.696 | Destabilizing | 0.991 | D | 0.386 | neutral | None | None | None | None | I |
| A/L | 0.2365 | likely_benign | 0.2057 | benign | -0.221 | Destabilizing | 0.759 | D | 0.345 | neutral | None | None | None | None | I |
| A/M | 0.2944 | likely_benign | 0.2529 | benign | -0.52 | Destabilizing | 0.759 | D | 0.335 | neutral | None | None | None | None | I |
| A/N | 0.3785 | ambiguous | 0.349 | ambiguous | -0.547 | Destabilizing | 0.991 | D | 0.481 | neutral | None | None | None | None | I |
| A/P | 0.7386 | likely_pathogenic | 0.7058 | pathogenic | -0.258 | Destabilizing | 0.996 | D | 0.41 | neutral | N | 0.499346828 | None | None | I |
| A/Q | 0.4514 | ambiguous | 0.4354 | ambiguous | -0.691 | Destabilizing | 0.991 | D | 0.416 | neutral | None | None | None | None | I |
| A/R | 0.7312 | likely_pathogenic | 0.6897 | pathogenic | -0.319 | Destabilizing | 0.991 | D | 0.41 | neutral | None | None | None | None | I |
| A/S | 0.1234 | likely_benign | 0.109 | benign | -0.804 | Destabilizing | 0.852 | D | 0.39 | neutral | N | 0.448360648 | None | None | I |
| A/T | 0.1491 | likely_benign | 0.1288 | benign | -0.769 | Destabilizing | 0.134 | N | 0.212 | neutral | N | 0.433468553 | None | None | I |
| A/V | 0.1979 | likely_benign | 0.1618 | benign | -0.258 | Destabilizing | 0.704 | D | 0.33 | neutral | N | 0.434660632 | None | None | I |
| A/W | 0.8699 | likely_pathogenic | 0.8617 | pathogenic | -0.954 | Destabilizing | 0.999 | D | 0.572 | neutral | None | None | None | None | I |
| A/Y | 0.5883 | likely_pathogenic | 0.5502 | ambiguous | -0.565 | Destabilizing | 0.997 | D | 0.461 | 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.