Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32416 | 97471;97472;97473 | chr2:178542510;178542509;178542508 | chr2:179407237;179407236;179407235 |
| N2AB | 30775 | 92548;92549;92550 | chr2:178542510;178542509;178542508 | chr2:179407237;179407236;179407235 |
| N2A | 29848 | 89767;89768;89769 | chr2:178542510;178542509;178542508 | chr2:179407237;179407236;179407235 |
| N2B | 23351 | 70276;70277;70278 | chr2:178542510;178542509;178542508 | chr2:179407237;179407236;179407235 |
| Novex-1 | 23476 | 70651;70652;70653 | chr2:178542510;178542509;178542508 | chr2:179407237;179407236;179407235 |
| Novex-2 | 23543 | 70852;70853;70854 | chr2:178542510;178542509;178542508 | chr2:179407237;179407236;179407235 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs377412567  |
-0.251 | 0.811 | D | 0.663 | 0.377 | None | gnomAD-2.1.1 | 6.09E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.17873E-04 | 1.40964E-04 |
| S/L | rs377412567 |
-0.251 | 0.811 | D | 0.663 | 0.377 | None | gnomAD-3.1.2 | 8.54E-05 | None | None | None | None | N | None | 4.83E-05 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47024E-04 | 0 | 0 |
| S/L | rs377412567 |
-0.251 | 0.811 | D | 0.663 | 0.377 | None | gnomAD-4.0.0 | 1.48897E-04 | None | None | None | None | N | None | 2.6708E-05 | 1.6675E-05 | None | 0 | 0 | None | 0 | 0 | 1.93508E-04 | 0 | 1.44254E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1033 | likely_benign | 0.1007 | benign | -0.558 | Destabilizing | 0.78 | D | 0.572 | neutral | D | 0.524567773 | None | None | N |
| S/C | 0.1095 | likely_benign | 0.0997 | benign | -0.939 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | N |
| S/D | 0.6977 | likely_pathogenic | 0.7036 | pathogenic | -1.85 | Destabilizing | 0.996 | D | 0.622 | neutral | None | None | None | None | N |
| S/E | 0.7759 | likely_pathogenic | 0.7777 | pathogenic | -1.79 | Destabilizing | 0.959 | D | 0.597 | neutral | None | None | None | None | N |
| S/F | 0.2621 | likely_benign | 0.2289 | benign | -0.901 | Destabilizing | 0.076 | N | 0.523 | neutral | None | None | None | None | N |
| S/G | 0.1374 | likely_benign | 0.1194 | benign | -0.803 | Destabilizing | 0.959 | D | 0.572 | neutral | None | None | None | None | N |
| S/H | 0.4048 | ambiguous | 0.4091 | ambiguous | -1.298 | Destabilizing | 0.976 | D | 0.712 | prob.delet. | None | None | None | None | N |
| S/I | 0.4375 | ambiguous | 0.4168 | ambiguous | -0.002 | Destabilizing | 0.952 | D | 0.736 | prob.delet. | None | None | None | None | N |
| S/K | 0.8981 | likely_pathogenic | 0.8964 | pathogenic | -0.674 | Destabilizing | 0.959 | D | 0.593 | neutral | None | None | None | None | N |
| S/L | 0.2304 | likely_benign | 0.2075 | benign | -0.002 | Destabilizing | 0.811 | D | 0.663 | neutral | D | 0.532555901 | None | None | N |
| S/M | 0.2423 | likely_benign | 0.2307 | benign | 0.169 | Stabilizing | 0.997 | D | 0.708 | prob.delet. | None | None | None | None | N |
| S/N | 0.2158 | likely_benign | 0.2146 | benign | -1.162 | Destabilizing | 0.988 | D | 0.614 | neutral | None | None | None | None | N |
| S/P | 0.9935 | likely_pathogenic | 0.9928 | pathogenic | -0.155 | Destabilizing | 0.995 | D | 0.763 | deleterious | D | 0.543912206 | None | None | N |
| S/Q | 0.6355 | likely_pathogenic | 0.6391 | pathogenic | -1.328 | Destabilizing | 0.996 | D | 0.665 | neutral | None | None | None | None | N |
| S/R | 0.8409 | likely_pathogenic | 0.8282 | pathogenic | -0.552 | Destabilizing | 0.988 | D | 0.766 | deleterious | None | None | None | None | N |
| S/T | 0.107 | likely_benign | 0.108 | benign | -0.883 | Destabilizing | 0.946 | D | 0.591 | neutral | N | 0.48296908 | None | None | N |
| S/V | 0.3565 | ambiguous | 0.3246 | benign | -0.155 | Destabilizing | 0.919 | D | 0.699 | prob.neutral | None | None | None | None | N |
| S/W | 0.4658 | ambiguous | 0.4297 | ambiguous | -1.057 | Destabilizing | 0.997 | D | 0.779 | deleterious | None | None | None | None | N |
| S/Y | 0.2451 | likely_benign | 0.2204 | benign | -0.635 | Destabilizing | 0.034 | N | 0.525 | 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.