Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3946 | 12061;12062;12063 | chr2:178741397;178741396;178741395 | chr2:179606124;179606123;179606122 |
| N2AB | 3629 | 11110;11111;11112 | chr2:178741397;178741396;178741395 | chr2:179606124;179606123;179606122 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3583 | 10972;10973;10974 | chr2:178741397;178741396;178741395 | chr2:179606124;179606123;179606122 |
| Novex-1 | 3708 | 11347;11348;11349 | chr2:178741397;178741396;178741395 | chr2:179606124;179606123;179606122 |
| Novex-2 | 3775 | 11548;11549;11550 | chr2:178741397;178741396;178741395 | chr2:179606124;179606123;179606122 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.565 | N | 0.517 | 0.206 | None | gnomAD-4.0.0 | 1.59107E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02389E-05 |
| P/S | rs970485392  |
-0.719 | 0.075 | N | 0.307 | 0.071 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs970485392 |
-0.719 | 0.075 | N | 0.307 | 0.071 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs970485392 |
-0.719 | 0.075 | N | 0.307 | 0.071 | None | gnomAD-4.0.0 | 4.33771E-06 | None | None | None | None | I | None | 8.00854E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60113E-05 |
| P/T | rs970485392 |
None | 0.565 | N | 0.481 | 0.063 | None | gnomAD-4.0.0 | 4.10504E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39658E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0663 | likely_benign | 0.066 | benign | -0.707 | Destabilizing | 0.008 | N | 0.341 | neutral | N | 0.435694601 | None | None | I |
| P/C | 0.452 | ambiguous | 0.4389 | ambiguous | -0.565 | Destabilizing | 0.989 | D | 0.657 | neutral | None | None | None | None | I |
| P/D | 0.3021 | likely_benign | 0.2918 | benign | -0.625 | Destabilizing | 0.923 | D | 0.475 | neutral | None | None | None | None | I |
| P/E | 0.2301 | likely_benign | 0.2103 | benign | -0.688 | Destabilizing | 0.775 | D | 0.481 | neutral | None | None | None | None | I |
| P/F | 0.5192 | ambiguous | 0.4884 | ambiguous | -0.694 | Destabilizing | 0.961 | D | 0.639 | neutral | None | None | None | None | I |
| P/G | 0.2179 | likely_benign | 0.2181 | benign | -0.907 | Destabilizing | 0.633 | D | 0.483 | neutral | None | None | None | None | I |
| P/H | 0.2159 | likely_benign | 0.2001 | benign | -0.418 | Destabilizing | 0.989 | D | 0.618 | neutral | None | None | None | None | I |
| P/I | 0.3712 | ambiguous | 0.3512 | ambiguous | -0.298 | Destabilizing | 0.923 | D | 0.625 | neutral | None | None | None | None | I |
| P/K | 0.2842 | likely_benign | 0.2492 | benign | -0.654 | Destabilizing | 0.633 | D | 0.48 | neutral | None | None | None | None | I |
| P/L | 0.1758 | likely_benign | 0.1602 | benign | -0.298 | Destabilizing | 0.565 | D | 0.517 | neutral | N | 0.461829693 | None | None | I |
| P/M | 0.3567 | ambiguous | 0.335 | benign | -0.418 | Destabilizing | 0.996 | D | 0.619 | neutral | None | None | None | None | I |
| P/N | 0.2605 | likely_benign | 0.2463 | benign | -0.382 | Destabilizing | 0.858 | D | 0.568 | neutral | None | None | None | None | I |
| P/Q | 0.1685 | likely_benign | 0.1548 | benign | -0.582 | Destabilizing | 0.901 | D | 0.551 | neutral | N | 0.466732411 | None | None | I |
| P/R | 0.1891 | likely_benign | 0.1632 | benign | -0.148 | Destabilizing | 0.018 | N | 0.413 | neutral | N | 0.501054754 | None | None | I |
| P/S | 0.1086 | likely_benign | 0.105 | benign | -0.744 | Destabilizing | 0.075 | N | 0.307 | neutral | N | 0.444456554 | None | None | I |
| P/T | 0.1081 | likely_benign | 0.1022 | benign | -0.704 | Destabilizing | 0.565 | D | 0.481 | neutral | N | 0.438870361 | None | None | I |
| P/V | 0.238 | likely_benign | 0.2284 | benign | -0.399 | Destabilizing | 0.858 | D | 0.487 | neutral | None | None | None | None | I |
| P/W | 0.6169 | likely_pathogenic | 0.5911 | pathogenic | -0.823 | Destabilizing | 0.996 | D | 0.691 | prob.neutral | None | None | None | None | I |
| P/Y | 0.4069 | ambiguous | 0.3899 | ambiguous | -0.525 | Destabilizing | 0.987 | D | 0.64 | 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.