Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22904 | 68935;68936;68937 | chr2:178577716;178577715;178577714 | chr2:179442443;179442442;179442441 |
| N2AB | 21263 | 64012;64013;64014 | chr2:178577716;178577715;178577714 | chr2:179442443;179442442;179442441 |
| N2A | 20336 | 61231;61232;61233 | chr2:178577716;178577715;178577714 | chr2:179442443;179442442;179442441 |
| N2B | 13839 | 41740;41741;41742 | chr2:178577716;178577715;178577714 | chr2:179442443;179442442;179442441 |
| Novex-1 | 13964 | 42115;42116;42117 | chr2:178577716;178577715;178577714 | chr2:179442443;179442442;179442441 |
| Novex-2 | 14031 | 42316;42317;42318 | chr2:178577716;178577715;178577714 | chr2:179442443;179442442;179442441 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs779476151  |
-0.12 | 0.997 | N | 0.721 | 0.446 | None | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 1.29266E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs779476151 |
-0.12 | 0.997 | N | 0.721 | 0.446 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs779476151 |
-0.12 | 0.997 | N | 0.721 | 0.446 | None | gnomAD-4.0.0 | 3.8454E-06 | None | None | None | None | I | None | 5.07614E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs779476151 |
-0.205 | 0.1 | N | 0.29 | 0.322 | 0.269558022972 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| T/N | rs779476151 |
-0.205 | 0.1 | N | 0.29 | 0.322 | 0.269558022972 | gnomAD-4.0.0 | 3.18441E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71932E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0948 | likely_benign | 0.1035 | benign | -0.672 | Destabilizing | 0.939 | D | 0.443 | neutral | N | 0.479272504 | None | None | I |
| T/C | 0.434 | ambiguous | 0.4761 | ambiguous | -0.335 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | None | None | None | None | I |
| T/D | 0.4064 | ambiguous | 0.4631 | ambiguous | 0.059 | Stabilizing | 0.91 | D | 0.603 | neutral | None | None | None | None | I |
| T/E | 0.3357 | likely_benign | 0.3883 | ambiguous | 0.004 | Stabilizing | 0.953 | D | 0.623 | neutral | None | None | None | None | I |
| T/F | 0.3592 | ambiguous | 0.4171 | ambiguous | -1.026 | Destabilizing | 0.998 | D | 0.771 | deleterious | None | None | None | None | I |
| T/G | 0.2 | likely_benign | 0.2035 | benign | -0.849 | Destabilizing | 0.91 | D | 0.621 | neutral | None | None | None | None | I |
| T/H | 0.2789 | likely_benign | 0.3209 | benign | -1.165 | Destabilizing | 0.998 | D | 0.754 | deleterious | None | None | None | None | I |
| T/I | 0.2665 | likely_benign | 0.3243 | benign | -0.315 | Destabilizing | 0.997 | D | 0.721 | prob.delet. | N | 0.49798587 | None | None | I |
| T/K | 0.1988 | likely_benign | 0.2348 | benign | -0.556 | Destabilizing | 0.986 | D | 0.638 | neutral | None | None | None | None | I |
| T/L | 0.1316 | likely_benign | 0.1487 | benign | -0.315 | Destabilizing | 0.976 | D | 0.603 | neutral | None | None | None | None | I |
| T/M | 0.1051 | likely_benign | 0.1094 | benign | 0.03 | Stabilizing | 0.999 | D | 0.696 | prob.neutral | None | None | None | None | I |
| T/N | 0.1133 | likely_benign | 0.127 | benign | -0.348 | Destabilizing | 0.1 | N | 0.29 | neutral | N | 0.488133594 | None | None | I |
| T/P | 0.1133 | likely_benign | 0.1247 | benign | -0.404 | Destabilizing | 0.046 | N | 0.339 | neutral | N | 0.483538465 | None | None | I |
| T/Q | 0.2328 | likely_benign | 0.2568 | benign | -0.59 | Destabilizing | 0.993 | D | 0.719 | prob.delet. | None | None | None | None | I |
| T/R | 0.204 | likely_benign | 0.2423 | benign | -0.27 | Destabilizing | 0.986 | D | 0.711 | prob.delet. | None | None | None | None | I |
| T/S | 0.1029 | likely_benign | 0.1077 | benign | -0.615 | Destabilizing | 0.885 | D | 0.45 | neutral | N | 0.488062681 | None | None | I |
| T/V | 0.1939 | likely_benign | 0.2255 | benign | -0.404 | Destabilizing | 0.976 | D | 0.501 | neutral | None | None | None | None | I |
| T/W | 0.675 | likely_pathogenic | 0.7339 | pathogenic | -0.96 | Destabilizing | 0.999 | D | 0.708 | prob.delet. | None | None | None | None | I |
| T/Y | 0.3662 | ambiguous | 0.4339 | ambiguous | -0.719 | Destabilizing | 0.998 | D | 0.772 | deleterious | 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.