Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23008 | 69247;69248;69249 | chr2:178577313;178577312;178577311 | chr2:179442040;179442039;179442038 |
| N2AB | 21367 | 64324;64325;64326 | chr2:178577313;178577312;178577311 | chr2:179442040;179442039;179442038 |
| N2A | 20440 | 61543;61544;61545 | chr2:178577313;178577312;178577311 | chr2:179442040;179442039;179442038 |
| N2B | 13943 | 42052;42053;42054 | chr2:178577313;178577312;178577311 | chr2:179442040;179442039;179442038 |
| Novex-1 | 14068 | 42427;42428;42429 | chr2:178577313;178577312;178577311 | chr2:179442040;179442039;179442038 |
| Novex-2 | 14135 | 42628;42629;42630 | chr2:178577313;178577312;178577311 | chr2:179442040;179442039;179442038 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs2046652524  |
None | 1.0 | N | 0.683 | 0.336 | 0.229264304666 | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/N | rs2046652524 |
None | 1.0 | N | 0.683 | 0.336 | 0.229264304666 | gnomAD-4.0.0 | 1.36874E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79924E-06 | 0 | 0 |
| K/T | rs765816052 |
-1.117 | 1.0 | N | 0.706 | 0.556 | 0.565612946506 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| K/T | rs765816052 |
-1.117 | 1.0 | N | 0.706 | 0.556 | 0.565612946506 | gnomAD-4.0.0 | 1.59211E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85976E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.6729 | likely_pathogenic | 0.6581 | pathogenic | -0.733 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| K/C | 0.8402 | likely_pathogenic | 0.8265 | pathogenic | -0.752 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| K/D | 0.8526 | likely_pathogenic | 0.85 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| K/E | 0.5135 | ambiguous | 0.4966 | ambiguous | 0.143 | Stabilizing | 0.999 | D | 0.536 | neutral | N | 0.510393328 | None | None | N |
| K/F | 0.938 | likely_pathogenic | 0.9313 | pathogenic | -0.49 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| K/G | 0.7611 | likely_pathogenic | 0.7586 | pathogenic | -1.092 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| K/H | 0.4514 | ambiguous | 0.4313 | ambiguous | -1.422 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | N |
| K/I | 0.6815 | likely_pathogenic | 0.6578 | pathogenic | 0.197 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| K/L | 0.648 | likely_pathogenic | 0.6385 | pathogenic | 0.197 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| K/M | 0.5153 | ambiguous | 0.5029 | ambiguous | 0.109 | Stabilizing | 1.0 | D | 0.635 | neutral | N | 0.493672182 | None | None | N |
| K/N | 0.7092 | likely_pathogenic | 0.7025 | pathogenic | -0.438 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.496714742 | None | None | N |
| K/P | 0.7777 | likely_pathogenic | 0.7937 | pathogenic | -0.083 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| K/Q | 0.2448 | likely_benign | 0.2331 | benign | -0.523 | Destabilizing | 1.0 | D | 0.67 | neutral | D | 0.533846191 | None | None | N |
| K/R | 0.0969 | likely_benign | 0.096 | benign | -0.548 | Destabilizing | 0.999 | D | 0.495 | neutral | N | 0.501851203 | None | None | N |
| K/S | 0.6952 | likely_pathogenic | 0.6826 | pathogenic | -1.19 | Destabilizing | 0.999 | D | 0.57 | neutral | None | None | None | None | N |
| K/T | 0.3673 | ambiguous | 0.3568 | ambiguous | -0.856 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | N | 0.511625479 | None | None | N |
| K/V | 0.666 | likely_pathogenic | 0.6369 | pathogenic | -0.083 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| K/W | 0.904 | likely_pathogenic | 0.8994 | pathogenic | -0.313 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| K/Y | 0.8375 | likely_pathogenic | 0.8277 | pathogenic | -0.016 | Destabilizing | 1.0 | D | 0.695 | prob.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.