Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22860 | 68803;68804;68805 | chr2:178577848;178577847;178577846 | chr2:179442575;179442574;179442573 |
| N2AB | 21219 | 63880;63881;63882 | chr2:178577848;178577847;178577846 | chr2:179442575;179442574;179442573 |
| N2A | 20292 | 61099;61100;61101 | chr2:178577848;178577847;178577846 | chr2:179442575;179442574;179442573 |
| N2B | 13795 | 41608;41609;41610 | chr2:178577848;178577847;178577846 | chr2:179442575;179442574;179442573 |
| Novex-1 | 13920 | 41983;41984;41985 | chr2:178577848;178577847;178577846 | chr2:179442575;179442574;179442573 |
| Novex-2 | 13987 | 42184;42185;42186 | chr2:178577848;178577847;178577846 | chr2:179442575;179442574;179442573 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | rs754466645  |
-0.342 | 0.999 | D | 0.543 | 0.321 | 0.680330652673 | gnomAD-2.1.1 | 4.2E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.21E-06 | 0 |
| L/I | rs754466645 |
-0.342 | 0.999 | D | 0.543 | 0.321 | 0.680330652673 | gnomAD-4.0.0 | 1.58807E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.99118E-05 | 0 | 1.67358E-05 |
| L/P | rs751068065 |
-1.384 | 1.0 | D | 0.907 | 0.786 | 0.912988770058 | gnomAD-2.1.1 | 4.21E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.69E-05 | None | 0 | None | 0 | 0 | 0 |
| L/P | rs751068065 |
-1.384 | 1.0 | D | 0.907 | 0.786 | 0.912988770058 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9607 | likely_pathogenic | 0.9577 | pathogenic | -2.682 | Highly Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | N |
| L/C | 0.9331 | likely_pathogenic | 0.9289 | pathogenic | -1.636 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| L/D | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.428 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| L/E | 0.9985 | likely_pathogenic | 0.9983 | pathogenic | -3.1 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| L/F | 0.8054 | likely_pathogenic | 0.8071 | pathogenic | -1.622 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.532079056 | None | None | N |
| L/G | 0.9958 | likely_pathogenic | 0.9954 | pathogenic | -3.277 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| L/H | 0.9968 | likely_pathogenic | 0.9964 | pathogenic | -3.057 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | D | 0.572682112 | None | None | N |
| L/I | 0.1463 | likely_benign | 0.1384 | benign | -0.877 | Destabilizing | 0.999 | D | 0.543 | neutral | D | 0.523124978 | None | None | N |
| L/K | 0.9975 | likely_pathogenic | 0.9973 | pathogenic | -2.058 | Highly Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| L/M | 0.3179 | likely_benign | 0.3174 | benign | -1.003 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| L/N | 0.9984 | likely_pathogenic | 0.9982 | pathogenic | -2.839 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| L/P | 0.9984 | likely_pathogenic | 0.9982 | pathogenic | -1.472 | Destabilizing | 1.0 | D | 0.907 | deleterious | D | 0.572682113 | None | None | N |
| L/Q | 0.9942 | likely_pathogenic | 0.9936 | pathogenic | -2.44 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| L/R | 0.9945 | likely_pathogenic | 0.9938 | pathogenic | -2.216 | Highly Destabilizing | 1.0 | D | 0.885 | deleterious | D | 0.572682112 | None | None | N |
| L/S | 0.9961 | likely_pathogenic | 0.9955 | pathogenic | -3.29 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| L/T | 0.9748 | likely_pathogenic | 0.9718 | pathogenic | -2.8 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| L/V | 0.1734 | likely_benign | 0.166 | benign | -1.472 | Destabilizing | 0.999 | D | 0.565 | neutral | N | 0.477110138 | None | None | N |
| L/W | 0.9926 | likely_pathogenic | 0.992 | pathogenic | -2.004 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| L/Y | 0.9903 | likely_pathogenic | 0.9898 | pathogenic | -1.821 | Destabilizing | 1.0 | D | 0.798 | deleterious | 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.