Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30138 | 90637;90638;90639 | chr2:178552488;178552487;178552486 | chr2:179417215;179417214;179417213 |
| N2AB | 28497 | 85714;85715;85716 | chr2:178552488;178552487;178552486 | chr2:179417215;179417214;179417213 |
| N2A | 27570 | 82933;82934;82935 | chr2:178552488;178552487;178552486 | chr2:179417215;179417214;179417213 |
| N2B | 21073 | 63442;63443;63444 | chr2:178552488;178552487;178552486 | chr2:179417215;179417214;179417213 |
| Novex-1 | 21198 | 63817;63818;63819 | chr2:178552488;178552487;178552486 | chr2:179417215;179417214;179417213 |
| Novex-2 | 21265 | 64018;64019;64020 | chr2:178552488;178552487;178552486 | chr2:179417215;179417214;179417213 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/R | rs1225356759  |
-0.244 | 0.942 | N | 0.649 | 0.281 | 0.520694202979 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| G/R | rs1225356759 |
-0.244 | 0.942 | N | 0.649 | 0.281 | 0.520694202979 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| G/R | rs1225356759 |
-0.244 | 0.942 | N | 0.649 | 0.281 | 0.520694202979 | gnomAD-4.0.0 | 6.41534E-06 | None | None | None | None | I | None | 1.6921E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.59256E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1292 | likely_benign | 0.119 | benign | -0.362 | Destabilizing | 0.698 | D | 0.547 | neutral | N | 0.475411176 | None | None | I |
| G/C | 0.2451 | likely_benign | 0.2383 | benign | -1.112 | Destabilizing | 0.998 | D | 0.706 | prob.neutral | None | None | None | None | I |
| G/D | 0.1742 | likely_benign | 0.1499 | benign | -0.787 | Destabilizing | 0.754 | D | 0.524 | neutral | None | None | None | None | I |
| G/E | 0.2002 | likely_benign | 0.169 | benign | -0.934 | Destabilizing | 0.032 | N | 0.399 | neutral | N | 0.422288767 | None | None | I |
| G/F | 0.5427 | ambiguous | 0.4953 | ambiguous | -1.032 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | None | None | None | None | I |
| G/H | 0.3303 | likely_benign | 0.3163 | benign | -0.355 | Destabilizing | 0.994 | D | 0.625 | neutral | None | None | None | None | I |
| G/I | 0.3413 | ambiguous | 0.3186 | benign | -0.559 | Destabilizing | 0.978 | D | 0.698 | prob.neutral | None | None | None | None | I |
| G/K | 0.364 | ambiguous | 0.3338 | benign | -0.893 | Destabilizing | 0.754 | D | 0.56 | neutral | None | None | None | None | I |
| G/L | 0.3881 | ambiguous | 0.3586 | ambiguous | -0.559 | Destabilizing | 0.956 | D | 0.703 | prob.neutral | None | None | None | None | I |
| G/M | 0.4104 | ambiguous | 0.3909 | ambiguous | -0.781 | Destabilizing | 0.998 | D | 0.687 | prob.neutral | None | None | None | None | I |
| G/N | 0.1962 | likely_benign | 0.1952 | benign | -0.643 | Destabilizing | 0.076 | N | 0.385 | neutral | None | None | None | None | I |
| G/P | 0.7987 | likely_pathogenic | 0.762 | pathogenic | -0.467 | Destabilizing | 0.978 | D | 0.643 | neutral | None | None | None | None | I |
| G/Q | 0.2763 | likely_benign | 0.2502 | benign | -0.903 | Destabilizing | 0.915 | D | 0.651 | neutral | None | None | None | None | I |
| G/R | 0.2831 | likely_benign | 0.2583 | benign | -0.408 | Destabilizing | 0.942 | D | 0.649 | neutral | N | 0.446301777 | None | None | I |
| G/S | 0.1114 | likely_benign | 0.1071 | benign | -0.78 | Destabilizing | 0.754 | D | 0.544 | neutral | None | None | None | None | I |
| G/T | 0.1631 | likely_benign | 0.1582 | benign | -0.86 | Destabilizing | 0.956 | D | 0.568 | neutral | None | None | None | None | I |
| G/V | 0.2253 | likely_benign | 0.2048 | benign | -0.467 | Destabilizing | 0.942 | D | 0.704 | prob.neutral | N | 0.432911193 | None | None | I |
| G/W | 0.4523 | ambiguous | 0.4092 | ambiguous | -1.133 | Destabilizing | 0.997 | D | 0.666 | neutral | N | 0.476971401 | None | None | I |
| G/Y | 0.3823 | ambiguous | 0.3533 | ambiguous | -0.837 | Destabilizing | 0.993 | D | 0.687 | prob.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.