Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35955 | 108088;108089;108090 | chr2:178527125;178527124;178527123 | chr2:179391852;179391851;179391850 |
| N2AB | 34314 | 103165;103166;103167 | chr2:178527125;178527124;178527123 | chr2:179391852;179391851;179391850 |
| N2A | 33387 | 100384;100385;100386 | chr2:178527125;178527124;178527123 | chr2:179391852;179391851;179391850 |
| N2B | 26890 | 80893;80894;80895 | chr2:178527125;178527124;178527123 | chr2:179391852;179391851;179391850 |
| Novex-1 | 27015 | 81268;81269;81270 | chr2:178527125;178527124;178527123 | chr2:179391852;179391851;179391850 |
| Novex-2 | 27082 | 81469;81470;81471 | chr2:178527125;178527124;178527123 | chr2:179391852;179391851;179391850 |
| 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 | rs370267738  |
None | 1.0 | N | 0.721 | 0.472 | 0.619797697146 | gnomAD-4.0.0 | 6.84145E-07 | None | None | None | -1.454(OBSL1) -0.348(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99404E-07 | 0 | 0 |
| T/N | rs370267738 |
-1.535 | 0.884 | N | 0.391 | 0.349 | None | gnomAD-2.1.1 | 1.2E-05 | None | None | None | -1.246(OBSL1) -0.793(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.65E-05 | 0 |
| T/N | rs370267738 |
-1.535 | 0.884 | N | 0.391 | 0.349 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | -1.246(OBSL1) -0.793(OBSCN) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/N | rs370267738 |
-1.535 | 0.884 | N | 0.391 | 0.349 | None | gnomAD-4.0.0 | 7.43567E-06 | None | None | None | -1.246(OBSL1) -0.793(OBSCN) | N | None | 0 | 1.66678E-05 | None | 0 | 0 | None | 0 | 0 | 9.32295E-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 | 0.3143 | likely_benign | 0.2989 | benign | -1.179 | Destabilizing | 0.998 | D | 0.484 | neutral | N | 0.508475208 | None | -1.189(OBSL1) -0.107(OBSCN) | N |
| T/C | 0.8715 | likely_pathogenic | 0.8671 | pathogenic | -1.019 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | -1.178(OBSL1) -0.562(OBSCN) | N |
| T/D | 0.9478 | likely_pathogenic | 0.9324 | pathogenic | -1.837 | Destabilizing | 0.998 | D | 0.638 | neutral | None | None | None | -0.636(OBSL1) -0.489(OBSCN) | N |
| T/E | 0.8794 | likely_pathogenic | 0.8544 | pathogenic | -1.643 | Destabilizing | 0.999 | D | 0.642 | neutral | None | None | None | -0.756(OBSL1) -0.628(OBSCN) | N |
| T/F | 0.8879 | likely_pathogenic | 0.8661 | pathogenic | -0.784 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | -1.22(OBSL1) -0.24(OBSCN) | N |
| T/G | 0.8367 | likely_pathogenic | 0.8303 | pathogenic | -1.589 | Destabilizing | 0.997 | D | 0.605 | neutral | None | None | None | -1.113(OBSL1) -0.05(OBSCN) | N |
| T/H | 0.802 | likely_pathogenic | 0.768 | pathogenic | -1.722 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | -0.824(OBSL1) 0.304(OBSCN) | N |
| T/I | 0.7222 | likely_pathogenic | 0.6817 | pathogenic | -0.106 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.494854405 | None | -1.454(OBSL1) -0.348(OBSCN) | N |
| T/K | 0.7862 | likely_pathogenic | 0.7237 | pathogenic | -0.791 | Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | -1.962(OBSL1) -1.096(OBSCN) | N |
| T/L | 0.4767 | ambiguous | 0.4379 | ambiguous | -0.106 | Destabilizing | 0.998 | D | 0.591 | neutral | None | None | None | -1.454(OBSL1) -0.348(OBSCN) | N |
| T/M | 0.3303 | likely_benign | 0.3038 | benign | -0.134 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | -1.126(OBSL1) -0.117(OBSCN) | N |
| T/N | 0.668 | likely_pathogenic | 0.6271 | pathogenic | -1.503 | Destabilizing | 0.884 | D | 0.391 | neutral | N | 0.4934356 | None | -1.246(OBSL1) -0.793(OBSCN) | N |
| T/P | 0.9077 | likely_pathogenic | 0.8715 | pathogenic | -0.433 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | D | 0.536494191 | None | -1.361(OBSL1) -0.257(OBSCN) | N |
| T/Q | 0.7612 | likely_pathogenic | 0.7264 | pathogenic | -1.286 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | -1.316(OBSL1) -0.771(OBSCN) | N |
| T/R | 0.7275 | likely_pathogenic | 0.6658 | pathogenic | -0.954 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | -1.947(OBSL1) -1.155(OBSCN) | N |
| T/S | 0.4061 | ambiguous | 0.4037 | ambiguous | -1.66 | Destabilizing | 0.996 | D | 0.499 | neutral | N | 0.508259887 | None | -1.471(OBSL1) -0.631(OBSCN) | N |
| T/V | 0.5044 | ambiguous | 0.4714 | ambiguous | -0.433 | Destabilizing | 1.0 | D | 0.553 | neutral | None | None | None | -1.361(OBSL1) -0.257(OBSCN) | N |
| T/W | 0.9614 | likely_pathogenic | 0.9547 | pathogenic | -0.981 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | -1.14(OBSL1) -0.289(OBSCN) | N |
| T/Y | 0.8543 | likely_pathogenic | 0.8202 | pathogenic | -0.603 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | -1.072(OBSL1) -0.037(OBSCN) | 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.