Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30646 | 92161;92162;92163 | chr2:178549786;178549785;178549784 | chr2:179414513;179414512;179414511 |
| N2AB | 29005 | 87238;87239;87240 | chr2:178549786;178549785;178549784 | chr2:179414513;179414512;179414511 |
| N2A | 28078 | 84457;84458;84459 | chr2:178549786;178549785;178549784 | chr2:179414513;179414512;179414511 |
| N2B | 21581 | 64966;64967;64968 | chr2:178549786;178549785;178549784 | chr2:179414513;179414512;179414511 |
| Novex-1 | 21706 | 65341;65342;65343 | chr2:178549786;178549785;178549784 | chr2:179414513;179414512;179414511 |
| Novex-2 | 21773 | 65542;65543;65544 | chr2:178549786;178549785;178549784 | chr2:179414513;179414512;179414511 |
| 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 | rs786205328  |
None | 1.0 | N | 0.679 | 0.465 | 0.215869574891 | gnomAD-4.0.0 | 1.37025E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80153E-06 | 0 | 0 |
| N/I | None | None | 1.0 | N | 0.739 | 0.531 | 0.559502987721 | gnomAD-4.0.0 | 1.37013E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80133E-06 | 0 | 0 |
| N/S | rs72648245 |
0.048 | 0.999 | N | 0.535 | 0.402 | None | gnomAD-2.1.1 | 7.21857E-04 | None | None | None | None | I | None | 6.20142E-03 | 9.34685E-04 | None | 0 | 5.13E-05 | None | 2.29268E-04 | None | 0 | 6.25E-05 | 4.22178E-04 |
| N/S | rs72648245 |
0.048 | 0.999 | N | 0.535 | 0.402 | None | gnomAD-3.1.2 | 1.84E-03 | None | None | None | None | I | None | 6.05607E-03 | 1.50642E-03 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 9.57854E-04 |
| N/S | rs72648245 |
0.048 | 0.999 | N | 0.535 | 0.402 | None | 1000 genomes | 1.19808E-03 | None | None | None | None | I | None | 2.3E-03 | 2.9E-03 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| N/S | rs72648245 |
0.048 | 0.999 | N | 0.535 | 0.402 | None | gnomAD-4.0.0 | 4.11908E-04 | None | None | None | None | I | None | 6.16E-03 | 1.16698E-03 | None | 0 | 2.23125E-05 | None | 1.5625E-05 | 1.65399E-04 | 7.044E-05 | 1.53866E-04 | 5.13034E-04 |
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 | 0.3519 | ambiguous | 0.3806 | ambiguous | -0.409 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| N/C | 0.3669 | ambiguous | 0.4173 | ambiguous | 0.395 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| N/D | 0.1346 | likely_benign | 0.1705 | benign | 0.031 | Stabilizing | 0.999 | D | 0.575 | neutral | N | 0.400032691 | None | None | I |
| N/E | 0.4339 | ambiguous | 0.4986 | ambiguous | 0.004 | Stabilizing | 0.999 | D | 0.682 | prob.neutral | None | None | None | None | I |
| N/F | 0.6116 | likely_pathogenic | 0.6808 | pathogenic | -0.755 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| N/G | 0.4583 | ambiguous | 0.4735 | ambiguous | -0.597 | Destabilizing | 0.999 | D | 0.533 | neutral | None | None | None | None | I |
| N/H | 0.1467 | likely_benign | 0.1767 | benign | -0.678 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.448848145 | None | None | I |
| N/I | 0.4188 | ambiguous | 0.4701 | ambiguous | 0.002 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.50658694 | None | None | I |
| N/K | 0.603 | likely_pathogenic | 0.6492 | pathogenic | 0.04 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.50004497 | None | None | I |
| N/L | 0.3344 | likely_benign | 0.3708 | ambiguous | 0.002 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| N/M | 0.4709 | ambiguous | 0.514 | ambiguous | 0.44 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| N/P | 0.9146 | likely_pathogenic | 0.9169 | pathogenic | -0.108 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| N/Q | 0.4523 | ambiguous | 0.4922 | ambiguous | -0.392 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| N/R | 0.5874 | likely_pathogenic | 0.6238 | pathogenic | 0.068 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| N/S | 0.1056 | likely_benign | 0.1149 | benign | -0.17 | Destabilizing | 0.999 | D | 0.535 | neutral | N | 0.459121067 | None | None | I |
| N/T | 0.2316 | likely_benign | 0.2426 | benign | -0.049 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | N | 0.491156128 | None | None | I |
| N/V | 0.3905 | ambiguous | 0.4316 | ambiguous | -0.108 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| N/W | 0.8349 | likely_pathogenic | 0.8678 | pathogenic | -0.727 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | I |
| N/Y | 0.2414 | likely_benign | 0.2926 | benign | -0.471 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.464566959 | 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.