Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29303 | 88132;88133;88134 | chr2:178557355;178557354;178557353 | chr2:179422082;179422081;179422080 |
| N2AB | 27662 | 83209;83210;83211 | chr2:178557355;178557354;178557353 | chr2:179422082;179422081;179422080 |
| N2A | 26735 | 80428;80429;80430 | chr2:178557355;178557354;178557353 | chr2:179422082;179422081;179422080 |
| N2B | 20238 | 60937;60938;60939 | chr2:178557355;178557354;178557353 | chr2:179422082;179422081;179422080 |
| Novex-1 | 20363 | 61312;61313;61314 | chr2:178557355;178557354;178557353 | chr2:179422082;179422081;179422080 |
| Novex-2 | 20430 | 61513;61514;61515 | chr2:178557355;178557354;178557353 | chr2:179422082;179422081;179422080 |
| 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/G | rs72648231  |
-0.938 | 0.948 | N | 0.391 | 0.189 | 0.259761712551 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/G | rs72648231 |
-0.938 | 0.948 | N | 0.391 | 0.189 | 0.259761712551 |
Begay (2015)
| None |
DCM 
|
het; co-inherited with LMNA mutant c.936G>A | None | None | N | WGS prioritisation; filtering with ANNOVAR; co-segregates within 2-generation family (n = 2, 2 affected (total 2)); LMNA variant also observed | None | None | None | None | None | None | None | None | None | None | None |
| S/G | rs72648231 |
-0.938 | 0.948 | N | 0.391 | 0.189 | 0.259761712551 | gnomAD-4.0.0 | 7.68472E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4355E-05 | 0 | 0 |
| S/I | rs1190785295 |
-0.142 | 0.999 | N | 0.678 | 0.341 | 0.589843679045 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/I | rs1190785295 |
-0.142 | 0.999 | N | 0.678 | 0.341 | 0.589843679045 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/I | rs1190785295 |
-0.142 | 0.999 | N | 0.678 | 0.341 | 0.589843679045 | gnomAD-4.0.0 | 6.40425E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19625E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.085 | likely_benign | 0.0837 | benign | -0.383 | Destabilizing | 0.96 | D | 0.413 | neutral | None | None | None | None | N |
| S/C | 0.126 | likely_benign | 0.1377 | benign | -0.396 | Destabilizing | 1.0 | D | 0.579 | neutral | D | 0.522079254 | None | None | N |
| S/D | 0.5295 | ambiguous | 0.5258 | ambiguous | 0.589 | Stabilizing | 0.967 | D | 0.359 | neutral | None | None | None | None | N |
| S/E | 0.6288 | likely_pathogenic | 0.6153 | pathogenic | 0.522 | Stabilizing | 0.983 | D | 0.405 | neutral | None | None | None | None | N |
| S/F | 0.3086 | likely_benign | 0.3181 | benign | -0.982 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| S/G | 0.1133 | likely_benign | 0.1171 | benign | -0.498 | Destabilizing | 0.948 | D | 0.391 | neutral | N | 0.475496615 | None | None | N |
| S/H | 0.3982 | ambiguous | 0.4135 | ambiguous | -0.781 | Destabilizing | 0.998 | D | 0.589 | neutral | None | None | None | None | N |
| S/I | 0.2 | likely_benign | 0.1624 | benign | -0.207 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | N | 0.429169093 | None | None | N |
| S/K | 0.7623 | likely_pathogenic | 0.7677 | pathogenic | -0.217 | Destabilizing | 0.983 | D | 0.397 | neutral | None | None | None | None | N |
| S/L | 0.1209 | likely_benign | 0.1233 | benign | -0.207 | Destabilizing | 0.998 | D | 0.54 | neutral | None | None | None | None | N |
| S/M | 0.1931 | likely_benign | 0.1957 | benign | -0.247 | Destabilizing | 1.0 | D | 0.565 | neutral | None | None | None | None | N |
| S/N | 0.1319 | likely_benign | 0.1358 | benign | -0.097 | Destabilizing | 0.054 | N | 0.154 | neutral | N | 0.434574913 | None | None | N |
| S/P | 0.5762 | likely_pathogenic | 0.5156 | ambiguous | -0.237 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | N |
| S/Q | 0.5303 | ambiguous | 0.5392 | ambiguous | -0.235 | Destabilizing | 0.998 | D | 0.519 | neutral | None | None | None | None | N |
| S/R | 0.7136 | likely_pathogenic | 0.7305 | pathogenic | -0.051 | Destabilizing | 0.994 | D | 0.568 | neutral | N | 0.448925503 | None | None | N |
| S/T | 0.0723 | likely_benign | 0.0733 | benign | -0.219 | Destabilizing | 0.978 | D | 0.37 | neutral | N | 0.423664486 | None | None | N |
| S/V | 0.1965 | likely_benign | 0.1955 | benign | -0.237 | Destabilizing | 0.998 | D | 0.657 | neutral | None | None | None | None | N |
| S/W | 0.5322 | ambiguous | 0.5566 | ambiguous | -1.011 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| S/Y | 0.2903 | likely_benign | 0.2943 | benign | -0.691 | Destabilizing | 0.999 | D | 0.68 | prob.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.