Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28760 | 86503;86504;86505 | chr2:178559854;178559853;178559852 | chr2:179424581;179424580;179424579 |
| N2AB | 27119 | 81580;81581;81582 | chr2:178559854;178559853;178559852 | chr2:179424581;179424580;179424579 |
| N2A | 26192 | 78799;78800;78801 | chr2:178559854;178559853;178559852 | chr2:179424581;179424580;179424579 |
| N2B | 19695 | 59308;59309;59310 | chr2:178559854;178559853;178559852 | chr2:179424581;179424580;179424579 |
| Novex-1 | 19820 | 59683;59684;59685 | chr2:178559854;178559853;178559852 | chr2:179424581;179424580;179424579 |
| Novex-2 | 19887 | 59884;59885;59886 | chr2:178559854;178559853;178559852 | chr2:179424581;179424580;179424579 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs756980643  |
-1.272 | 0.201 | N | 0.541 | 0.234 | 0.391470661076 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 9.92E-05 | 0 | 0 |
| M/I | rs756980643 |
-1.272 | 0.201 | N | 0.541 | 0.234 | 0.391470661076 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| M/I | rs756980643 |
-1.272 | 0.201 | N | 0.541 | 0.234 | 0.391470661076 | gnomAD-4.0.0 | 3.72323E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22826E-05 | None | 6.45453E-05 | 0 | 0 | 0 | 1.60143E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8112 | likely_pathogenic | 0.6985 | pathogenic | -1.89 | Destabilizing | 0.4 | N | 0.521 | neutral | None | None | None | None | N |
| M/C | 0.8814 | likely_pathogenic | 0.8486 | pathogenic | -1.377 | Destabilizing | 0.992 | D | 0.559 | neutral | None | None | None | None | N |
| M/D | 0.9483 | likely_pathogenic | 0.9317 | pathogenic | -0.457 | Destabilizing | 0.972 | D | 0.603 | neutral | None | None | None | None | N |
| M/E | 0.8743 | likely_pathogenic | 0.8277 | pathogenic | -0.384 | Destabilizing | 0.92 | D | 0.585 | neutral | None | None | None | None | N |
| M/F | 0.4586 | ambiguous | 0.4042 | ambiguous | -0.714 | Destabilizing | 0.005 | N | 0.301 | neutral | None | None | None | None | N |
| M/G | 0.8672 | likely_pathogenic | 0.8131 | pathogenic | -2.251 | Highly Destabilizing | 0.766 | D | 0.567 | neutral | None | None | None | None | N |
| M/H | 0.7868 | likely_pathogenic | 0.737 | pathogenic | -1.281 | Destabilizing | 0.992 | D | 0.566 | neutral | None | None | None | None | N |
| M/I | 0.7257 | likely_pathogenic | 0.5965 | pathogenic | -0.928 | Destabilizing | 0.201 | N | 0.541 | neutral | N | 0.473504234 | None | None | N |
| M/K | 0.6026 | likely_pathogenic | 0.519 | ambiguous | -0.714 | Destabilizing | 0.712 | D | 0.546 | neutral | N | 0.47862153 | None | None | N |
| M/L | 0.2077 | likely_benign | 0.1648 | benign | -0.928 | Destabilizing | 0.002 | N | 0.233 | neutral | N | 0.374108031 | None | None | N |
| M/N | 0.7781 | likely_pathogenic | 0.7044 | pathogenic | -0.641 | Destabilizing | 0.972 | D | 0.591 | neutral | None | None | None | None | N |
| M/P | 0.9721 | likely_pathogenic | 0.9472 | pathogenic | -1.223 | Destabilizing | 0.972 | D | 0.603 | neutral | None | None | None | None | N |
| M/Q | 0.5746 | likely_pathogenic | 0.5102 | ambiguous | -0.618 | Destabilizing | 0.972 | D | 0.614 | neutral | None | None | None | None | N |
| M/R | 0.6478 | likely_pathogenic | 0.5533 | ambiguous | -0.329 | Destabilizing | 0.896 | D | 0.591 | neutral | N | 0.47836804 | None | None | N |
| M/S | 0.7886 | likely_pathogenic | 0.6935 | pathogenic | -1.31 | Destabilizing | 0.766 | D | 0.529 | neutral | None | None | None | None | N |
| M/T | 0.6573 | likely_pathogenic | 0.5215 | ambiguous | -1.11 | Destabilizing | 0.549 | D | 0.523 | neutral | N | 0.468309058 | None | None | N |
| M/V | 0.3121 | likely_benign | 0.2301 | benign | -1.223 | Destabilizing | 0.201 | N | 0.465 | neutral | N | 0.466154188 | None | None | N |
| M/W | 0.7485 | likely_pathogenic | 0.7138 | pathogenic | -0.663 | Destabilizing | 0.992 | D | 0.553 | neutral | None | None | None | None | N |
| M/Y | 0.71 | likely_pathogenic | 0.6761 | pathogenic | -0.718 | Destabilizing | 0.447 | N | 0.562 | 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.