Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23352 | 70279;70280;70281 | chr2:178576078;178576077;178576076 | chr2:179440805;179440804;179440803 |
| N2AB | 21711 | 65356;65357;65358 | chr2:178576078;178576077;178576076 | chr2:179440805;179440804;179440803 |
| N2A | 20784 | 62575;62576;62577 | chr2:178576078;178576077;178576076 | chr2:179440805;179440804;179440803 |
| N2B | 14287 | 43084;43085;43086 | chr2:178576078;178576077;178576076 | chr2:179440805;179440804;179440803 |
| Novex-1 | 14412 | 43459;43460;43461 | chr2:178576078;178576077;178576076 | chr2:179440805;179440804;179440803 |
| Novex-2 | 14479 | 43660;43661;43662 | chr2:178576078;178576077;178576076 | chr2:179440805;179440804;179440803 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs755983483  |
-0.415 | 0.896 | N | 0.501 | 0.373 | 0.523342287332 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/G | rs755983483 |
-0.415 | 0.896 | N | 0.501 | 0.373 | 0.523342287332 | gnomAD-4.0.0 | 1.36862E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79917E-06 | 0 | 0 |
| R/I | None | None | 0.984 | D | 0.612 | 0.457 | 0.565096191312 | gnomAD-4.0.0 | 6.84313E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65684E-05 |
| R/K | rs555933077 |
0.039 | 0.011 | N | 0.255 | 0.129 | 0.262175524916 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.30727E-04 | None | 0 | 0 | 0 |
| R/K | rs555933077 |
0.039 | 0.011 | N | 0.255 | 0.129 | 0.262175524916 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| R/K | rs555933077 |
0.039 | 0.011 | N | 0.255 | 0.129 | 0.262175524916 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| R/K | rs555933077 |
0.039 | 0.011 | N | 0.255 | 0.129 | 0.262175524916 | gnomAD-4.0.0 | 6.15882E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.0436E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8459 | likely_pathogenic | 0.7765 | pathogenic | -0.074 | Destabilizing | 0.919 | D | 0.515 | neutral | None | None | None | None | I |
| R/C | 0.5736 | likely_pathogenic | 0.4701 | ambiguous | -0.179 | Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | I |
| R/D | 0.915 | likely_pathogenic | 0.8636 | pathogenic | -0.07 | Destabilizing | 0.976 | D | 0.499 | neutral | None | None | None | None | I |
| R/E | 0.7265 | likely_pathogenic | 0.6363 | pathogenic | -0.017 | Destabilizing | 0.851 | D | 0.496 | neutral | None | None | None | None | I |
| R/F | 0.9528 | likely_pathogenic | 0.9354 | pathogenic | -0.337 | Destabilizing | 0.996 | D | 0.609 | neutral | None | None | None | None | I |
| R/G | 0.6385 | likely_pathogenic | 0.532 | ambiguous | -0.255 | Destabilizing | 0.896 | D | 0.501 | neutral | N | 0.49885097 | None | None | I |
| R/H | 0.255 | likely_benign | 0.201 | benign | -0.713 | Destabilizing | 0.996 | D | 0.477 | neutral | None | None | None | None | I |
| R/I | 0.875 | likely_pathogenic | 0.8221 | pathogenic | 0.364 | Stabilizing | 0.984 | D | 0.612 | neutral | D | 0.523805343 | None | None | I |
| R/K | 0.1402 | likely_benign | 0.1107 | benign | -0.115 | Destabilizing | 0.011 | N | 0.255 | neutral | N | 0.397798541 | None | None | I |
| R/L | 0.739 | likely_pathogenic | 0.6624 | pathogenic | 0.364 | Stabilizing | 0.919 | D | 0.501 | neutral | None | None | None | None | I |
| R/M | 0.7703 | likely_pathogenic | 0.6846 | pathogenic | 0.026 | Stabilizing | 0.999 | D | 0.51 | neutral | None | None | None | None | I |
| R/N | 0.8435 | likely_pathogenic | 0.7771 | pathogenic | 0.15 | Stabilizing | 0.919 | D | 0.457 | neutral | None | None | None | None | I |
| R/P | 0.9585 | likely_pathogenic | 0.9412 | pathogenic | 0.238 | Stabilizing | 0.988 | D | 0.569 | neutral | None | None | None | None | I |
| R/Q | 0.2143 | likely_benign | 0.1706 | benign | 0.016 | Stabilizing | 0.919 | D | 0.483 | neutral | None | None | None | None | I |
| R/S | 0.8652 | likely_pathogenic | 0.8 | pathogenic | -0.23 | Destabilizing | 0.896 | D | 0.522 | neutral | N | 0.475838037 | None | None | I |
| R/T | 0.7239 | likely_pathogenic | 0.6312 | pathogenic | -0.05 | Destabilizing | 0.896 | D | 0.477 | neutral | N | 0.489442053 | None | None | I |
| R/V | 0.8739 | likely_pathogenic | 0.826 | pathogenic | 0.238 | Stabilizing | 0.988 | D | 0.564 | neutral | None | None | None | None | I |
| R/W | 0.6722 | likely_pathogenic | 0.6007 | pathogenic | -0.384 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | I |
| R/Y | 0.8413 | likely_pathogenic | 0.7877 | pathogenic | 0.025 | Stabilizing | 0.996 | D | 0.581 | 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.