Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32361 | 97306;97307;97308 | chr2:178542773;178542772;178542771 | chr2:179407500;179407499;179407498 |
| N2AB | 30720 | 92383;92384;92385 | chr2:178542773;178542772;178542771 | chr2:179407500;179407499;179407498 |
| N2A | 29793 | 89602;89603;89604 | chr2:178542773;178542772;178542771 | chr2:179407500;179407499;179407498 |
| N2B | 23296 | 70111;70112;70113 | chr2:178542773;178542772;178542771 | chr2:179407500;179407499;179407498 |
| Novex-1 | 23421 | 70486;70487;70488 | chr2:178542773;178542772;178542771 | chr2:179407500;179407499;179407498 |
| Novex-2 | 23488 | 70687;70688;70689 | chr2:178542773;178542772;178542771 | chr2:179407500;179407499;179407498 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | rs773186045  |
-2.449 | 0.351 | N | 0.514 | 0.279 | 0.696243023549 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.83E-06 | 1.40449E-04 |
| V/E | rs773186045 |
-2.449 | 0.351 | N | 0.514 | 0.279 | 0.696243023549 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/E | rs773186045 |
-2.449 | 0.351 | N | 0.514 | 0.279 | 0.696243023549 | gnomAD-4.0.0 | 4.95772E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93337E-06 | 0 | 1.60113E-05 |
| V/I | rs766538774 |
-0.646 | 0.101 | N | 0.389 | 0.051 | 0.378674557249 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.57E-05 | 0 |
| V/I | rs766538774 |
-0.646 | 0.101 | N | 0.389 | 0.051 | 0.378674557249 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 4.14079E-04 | 0 |
| V/I | rs766538774 |
-0.646 | 0.101 | N | 0.389 | 0.051 | 0.378674557249 | gnomAD-4.0.0 | 6.19706E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39043E-06 | 4.39155E-05 | 3.20215E-05 |
| V/L | rs766538774 |
-0.649 | 0.017 | N | 0.333 | 0.108 | 0.319114376414 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| V/L | rs766538774 |
-0.649 | 0.017 | N | 0.333 | 0.108 | 0.319114376414 | gnomAD-4.0.0 | 6.84197E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87294E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1316 | likely_benign | 0.1038 | benign | -1.666 | Destabilizing | 0.047 | N | 0.308 | neutral | N | 0.485822958 | None | None | N |
| V/C | 0.6521 | likely_pathogenic | 0.5898 | pathogenic | -1.032 | Destabilizing | 0.94 | D | 0.51 | neutral | None | None | None | None | N |
| V/D | 0.263 | likely_benign | 0.2121 | benign | -1.891 | Destabilizing | 0.418 | N | 0.585 | neutral | None | None | None | None | N |
| V/E | 0.2123 | likely_benign | 0.1685 | benign | -1.858 | Destabilizing | 0.351 | N | 0.514 | neutral | N | 0.480473066 | None | None | N |
| V/F | 0.1197 | likely_benign | 0.1031 | benign | -1.228 | Destabilizing | 0.001 | N | 0.201 | neutral | None | None | None | None | N |
| V/G | 0.1855 | likely_benign | 0.1543 | benign | -2.022 | Highly Destabilizing | 0.351 | N | 0.522 | neutral | N | 0.43048975 | None | None | N |
| V/H | 0.3975 | ambiguous | 0.3239 | benign | -1.725 | Destabilizing | 0.716 | D | 0.58 | neutral | None | None | None | None | N |
| V/I | 0.0821 | likely_benign | 0.0749 | benign | -0.764 | Destabilizing | 0.101 | N | 0.389 | neutral | N | 0.485302883 | None | None | N |
| V/K | 0.2899 | likely_benign | 0.2395 | benign | -1.499 | Destabilizing | 0.418 | N | 0.521 | neutral | None | None | None | None | N |
| V/L | 0.1768 | likely_benign | 0.1458 | benign | -0.764 | Destabilizing | 0.017 | N | 0.333 | neutral | N | 0.46344753 | None | None | N |
| V/M | 0.1183 | likely_benign | 0.0934 | benign | -0.512 | Destabilizing | 0.027 | N | 0.353 | neutral | None | None | None | None | N |
| V/N | 0.2077 | likely_benign | 0.1643 | benign | -1.334 | Destabilizing | 0.418 | N | 0.582 | neutral | None | None | None | None | N |
| V/P | 0.7633 | likely_pathogenic | 0.7339 | pathogenic | -1.032 | Destabilizing | 0.836 | D | 0.566 | neutral | None | None | None | None | N |
| V/Q | 0.2505 | likely_benign | 0.2071 | benign | -1.463 | Destabilizing | 0.836 | D | 0.566 | neutral | None | None | None | None | N |
| V/R | 0.2476 | likely_benign | 0.2086 | benign | -1.007 | Destabilizing | 0.716 | D | 0.594 | neutral | None | None | None | None | N |
| V/S | 0.1533 | likely_benign | 0.1182 | benign | -1.818 | Destabilizing | 0.129 | N | 0.469 | neutral | None | None | None | None | N |
| V/T | 0.111 | likely_benign | 0.0914 | benign | -1.683 | Destabilizing | 0.001 | N | 0.119 | neutral | None | None | None | None | N |
| V/W | 0.6083 | likely_pathogenic | 0.5464 | ambiguous | -1.547 | Destabilizing | 0.94 | D | 0.561 | neutral | None | None | None | None | N |
| V/Y | 0.34 | likely_benign | 0.2943 | benign | -1.247 | Destabilizing | 0.01 | N | 0.225 | 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.