TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19250	57973;57974;57975	chr2:178595606;178595605;178595604	chr2:179460333;179460332;179460331
N2AB	17609	53050;53051;53052	chr2:178595606;178595605;178595604	chr2:179460333;179460332;179460331
N2A	16682	50269;50270;50271	chr2:178595606;178595605;178595604	chr2:179460333;179460332;179460331
N2B	10185	30778;30779;30780	chr2:178595606;178595605;178595604	chr2:179460333;179460332;179460331
Novex-1	10310	31153;31154;31155	chr2:178595606;178595605;178595604	chr2:179460333;179460332;179460331
Novex-2	10377	31354;31355;31356	chr2:178595606;178595605;178595604	chr2:179460333;179460332;179460331
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-27
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4376
• Predicted PPI site: N

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
Q/P	None	None	0.106	N	0.393	0.194	0.165133752707	gnomAD-4.0.0	6.93904E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.08471E-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
Q/A	0.1313	likely_benign	0.1331	benign	-0.29	Destabilizing	0.007	N	0.257	neutral	None	None	None	None	N
Q/C	0.6409	likely_pathogenic	0.6643	pathogenic	0.124	Stabilizing	0.864	D	0.355	neutral	None	None	None	None	N
Q/D	0.3023	likely_benign	0.3464	ambiguous	0.016	Stabilizing	None	N	0.052	neutral	None	None	None	None	N
Q/E	0.0558	likely_benign	0.0559	benign	0.008	Stabilizing	None	N	0.041	neutral	N	0.362904029	None	None	N
Q/F	0.7409	likely_pathogenic	0.7552	pathogenic	-0.354	Destabilizing	0.628	D	0.395	neutral	None	None	None	None	N
Q/G	0.2559	likely_benign	0.2799	benign	-0.515	Destabilizing	0.031	N	0.225	neutral	None	None	None	None	N
Q/H	0.2352	likely_benign	0.2841	benign	-0.386	Destabilizing	0.295	N	0.391	neutral	N	0.458625209	None	None	N
Q/I	0.4207	ambiguous	0.4257	ambiguous	0.223	Stabilizing	0.356	N	0.452	neutral	None	None	None	None	N
Q/K	0.1153	likely_benign	0.1387	benign	-0.006	Destabilizing	0.005	N	0.247	neutral	N	0.444386475	None	None	N
Q/L	0.1683	likely_benign	0.1832	benign	0.223	Stabilizing	0.024	N	0.311	neutral	N	0.42559007	None	None	N
Q/M	0.3719	ambiguous	0.3766	ambiguous	0.483	Stabilizing	0.628	D	0.423	neutral	None	None	None	None	N
Q/N	0.2589	likely_benign	0.2773	benign	-0.381	Destabilizing	0.031	N	0.309	neutral	None	None	None	None	N
Q/P	0.0757	likely_benign	0.0952	benign	0.082	Stabilizing	0.106	N	0.393	neutral	N	0.338821156	None	None	N
Q/R	0.1326	likely_benign	0.1653	benign	0.146	Stabilizing	None	N	0.093	neutral	N	0.439423372	None	None	N
Q/S	0.1763	likely_benign	0.1751	benign	-0.401	Destabilizing	0.016	N	0.254	neutral	None	None	None	None	N
Q/T	0.1836	likely_benign	0.1978	benign	-0.244	Destabilizing	0.031	N	0.287	neutral	None	None	None	None	N
Q/V	0.2461	likely_benign	0.2559	benign	0.082	Stabilizing	0.072	N	0.307	neutral	None	None	None	None	N
Q/W	0.638	likely_pathogenic	0.7564	pathogenic	-0.287	Destabilizing	0.864	D	0.352	neutral	None	None	None	None	N
Q/Y	0.5204	ambiguous	0.591	pathogenic	-0.055	Destabilizing	0.628	D	0.433	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.