Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23660 | 71203;71204;71205 | chr2:178575154;178575153;178575152 | chr2:179439881;179439880;179439879 |
| N2AB | 22019 | 66280;66281;66282 | chr2:178575154;178575153;178575152 | chr2:179439881;179439880;179439879 |
| N2A | 21092 | 63499;63500;63501 | chr2:178575154;178575153;178575152 | chr2:179439881;179439880;179439879 |
| N2B | 14595 | 44008;44009;44010 | chr2:178575154;178575153;178575152 | chr2:179439881;179439880;179439879 |
| Novex-1 | 14720 | 44383;44384;44385 | chr2:178575154;178575153;178575152 | chr2:179439881;179439880;179439879 |
| Novex-2 | 14787 | 44584;44585;44586 | chr2:178575154;178575153;178575152 | chr2:179439881;179439880;179439879 |
| 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/L | rs570979108  |
0.256 | 0.996 | N | 0.593 | 0.376 | 0.469578130381 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| R/L | rs570979108 |
0.256 | 0.996 | N | 0.593 | 0.376 | 0.469578130381 | gnomAD-4.0.0 | 6.84727E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16144E-05 | 0 |
| R/Q | rs570979108 |
-0.078 | 0.999 | N | 0.561 | 0.266 | 0.307332253619 | gnomAD-2.1.1 | 2.84E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 3.41297E-04 | None | 0 | None | 0 | 8.98E-06 | 0 |
| R/Q | rs570979108 |
-0.078 | 0.999 | N | 0.561 | 0.266 | 0.307332253619 | gnomAD-4.0.0 | 2.67042E-05 | None | None | None | None | I | None | 0 | 2.24044E-05 | None | 0 | 1.52084E-04 | None | 0 | 0 | 2.42963E-05 | 1.16136E-05 | 6.63152E-05 |
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 | 0.8449 | likely_pathogenic | 0.8232 | pathogenic | 0.05 | Stabilizing | 0.985 | D | 0.595 | neutral | None | None | None | None | I |
| R/C | 0.2948 | likely_benign | 0.254 | benign | -0.248 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| R/D | 0.9691 | likely_pathogenic | 0.9676 | pathogenic | -0.323 | Destabilizing | 0.998 | D | 0.572 | neutral | None | None | None | None | I |
| R/E | 0.809 | likely_pathogenic | 0.7969 | pathogenic | -0.28 | Destabilizing | 0.985 | D | 0.571 | neutral | None | None | None | None | I |
| R/F | 0.7693 | likely_pathogenic | 0.7205 | pathogenic | -0.259 | Destabilizing | 0.999 | D | 0.617 | neutral | None | None | None | None | I |
| R/G | 0.7877 | likely_pathogenic | 0.7558 | pathogenic | -0.094 | Destabilizing | 0.996 | D | 0.593 | neutral | N | 0.484971994 | None | None | I |
| R/H | 0.1954 | likely_benign | 0.1596 | benign | -0.589 | Destabilizing | 0.999 | D | 0.562 | neutral | None | None | None | None | I |
| R/I | 0.4811 | ambiguous | 0.4537 | ambiguous | 0.383 | Stabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | I |
| R/K | 0.1811 | likely_benign | 0.1618 | benign | -0.174 | Destabilizing | 0.271 | N | 0.36 | neutral | None | None | None | None | I |
| R/L | 0.4905 | ambiguous | 0.4544 | ambiguous | 0.383 | Stabilizing | 0.996 | D | 0.593 | neutral | N | 0.491807568 | None | None | I |
| R/M | 0.5877 | likely_pathogenic | 0.5372 | ambiguous | -0.073 | Destabilizing | 1.0 | D | 0.571 | neutral | None | None | None | None | I |
| R/N | 0.8903 | likely_pathogenic | 0.8765 | pathogenic | -0.093 | Destabilizing | 0.998 | D | 0.555 | neutral | None | None | None | None | I |
| R/P | 0.9847 | likely_pathogenic | 0.9829 | pathogenic | 0.29 | Stabilizing | 1.0 | D | 0.6 | neutral | N | 0.508102679 | None | None | I |
| R/Q | 0.2107 | likely_benign | 0.1835 | benign | -0.124 | Destabilizing | 0.999 | D | 0.561 | neutral | N | 0.520916966 | None | None | I |
| R/S | 0.8574 | likely_pathogenic | 0.8368 | pathogenic | -0.26 | Destabilizing | 0.985 | D | 0.637 | neutral | None | None | None | None | I |
| R/T | 0.7224 | likely_pathogenic | 0.7007 | pathogenic | -0.111 | Destabilizing | 0.993 | D | 0.588 | neutral | None | None | None | None | I |
| R/V | 0.6382 | likely_pathogenic | 0.6134 | pathogenic | 0.29 | Stabilizing | 0.998 | D | 0.598 | neutral | None | None | None | None | I |
| R/W | 0.3528 | ambiguous | 0.2955 | benign | -0.44 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| R/Y | 0.5775 | likely_pathogenic | 0.5216 | ambiguous | -0.034 | Destabilizing | 0.999 | D | 0.611 | 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.