Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33478 | 100657;100658;100659 | chr2:178536315;178536314;178536313 | chr2:179401042;179401041;179401040 |
| N2AB | 31837 | 95734;95735;95736 | chr2:178536315;178536314;178536313 | chr2:179401042;179401041;179401040 |
| N2A | 30910 | 92953;92954;92955 | chr2:178536315;178536314;178536313 | chr2:179401042;179401041;179401040 |
| N2B | 24413 | 73462;73463;73464 | chr2:178536315;178536314;178536313 | chr2:179401042;179401041;179401040 |
| Novex-1 | 24538 | 73837;73838;73839 | chr2:178536315;178536314;178536313 | chr2:179401042;179401041;179401040 |
| Novex-2 | 24605 | 74038;74039;74040 | chr2:178536315;178536314;178536313 | chr2:179401042;179401041;179401040 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/C | rs1449345093  |
-0.984 | 1.0 | N | 0.706 | 0.378 | 0.218845423259 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| W/G | rs372304158 |
-2.745 | 0.999 | N | 0.65 | 0.53 | None | gnomAD-2.1.1 | 1.92912E-04 | None | None | None | None | N | None | 0 | 5.67E-05 | None | 0 | 0 | None | 9.81E-05 | None | 4E-05 | 3.59414E-04 | 2.81373E-04 |
| W/G | rs372304158 |
-2.745 | 0.999 | N | 0.65 | 0.53 | None | gnomAD-3.1.2 | 1.70819E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 3.52775E-04 | 0 | 4.78011E-04 |
| W/G | rs372304158 |
-2.745 | 0.999 | N | 0.65 | 0.53 | None | gnomAD-4.0.0 | 3.0367E-04 | None | None | None | None | N | None | 4.00406E-05 | 5.00217E-05 | None | 0 | 0 | None | 6.25528E-05 | 0 | 3.8906E-04 | 5.49028E-05 | 2.56189E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.5972 | likely_pathogenic | 0.6623 | pathogenic | -2.802 | Highly Destabilizing | 0.998 | D | 0.687 | prob.neutral | None | None | None | None | N |
| W/C | 0.8546 | likely_pathogenic | 0.8475 | pathogenic | -1.106 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | N | 0.463028164 | None | None | N |
| W/D | 0.899 | likely_pathogenic | 0.9229 | pathogenic | -1.206 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| W/E | 0.9372 | likely_pathogenic | 0.9515 | pathogenic | -1.134 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| W/F | 0.3041 | likely_benign | 0.287 | benign | -1.744 | Destabilizing | 0.967 | D | 0.469 | neutral | None | None | None | None | N |
| W/G | 0.5276 | ambiguous | 0.6282 | pathogenic | -3.0 | Highly Destabilizing | 0.999 | D | 0.65 | neutral | N | 0.492310921 | None | None | N |
| W/H | 0.8929 | likely_pathogenic | 0.8937 | pathogenic | -1.309 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| W/I | 0.7528 | likely_pathogenic | 0.7858 | pathogenic | -2.099 | Highly Destabilizing | 0.998 | D | 0.727 | prob.delet. | None | None | None | None | N |
| W/K | 0.9786 | likely_pathogenic | 0.9828 | pathogenic | -1.424 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | N |
| W/L | 0.6459 | likely_pathogenic | 0.6892 | pathogenic | -2.099 | Highly Destabilizing | 0.978 | D | 0.619 | neutral | N | 0.472164935 | None | None | N |
| W/M | 0.8448 | likely_pathogenic | 0.8476 | pathogenic | -1.509 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| W/N | 0.8691 | likely_pathogenic | 0.8921 | pathogenic | -1.742 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| W/P | 0.6019 | likely_pathogenic | 0.7125 | pathogenic | -2.347 | Highly Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| W/Q | 0.9712 | likely_pathogenic | 0.9742 | pathogenic | -1.727 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| W/R | 0.97 | likely_pathogenic | 0.973 | pathogenic | -0.863 | Destabilizing | 0.997 | D | 0.732 | prob.delet. | N | 0.465393678 | None | None | N |
| W/S | 0.5794 | likely_pathogenic | 0.6546 | pathogenic | -2.215 | Highly Destabilizing | 0.997 | D | 0.715 | prob.delet. | N | 0.472858368 | None | None | N |
| W/T | 0.7497 | likely_pathogenic | 0.798 | pathogenic | -2.102 | Highly Destabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | N |
| W/V | 0.7111 | likely_pathogenic | 0.7392 | pathogenic | -2.347 | Highly Destabilizing | 0.995 | D | 0.699 | prob.neutral | None | None | None | None | N |
| W/Y | 0.4333 | ambiguous | 0.4185 | ambiguous | -1.605 | Destabilizing | 0.437 | N | 0.389 | 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.