TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9764	29515;29516;29517	chr2:178706584;178706583;178706582	chr2:179571311;179571310;179571309
N2AB	9447	28564;28565;28566	chr2:178706584;178706583;178706582	chr2:179571311;179571310;179571309
N2A	8520	25783;25784;25785	chr2:178706584;178706583;178706582	chr2:179571311;179571310;179571309
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-83
• Domain position: 67
• Structural Position: 148
• Q(SASA): 0.5718
• 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
T/I	None	None	0.994	None	0.417	0.326	0.259272394797	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
T/S	None	None	0.287	None	0.174	0.16	0.0611884634855	gnomAD-4.0.0	1.36834E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	1.6564E-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
T/A	0.2939	likely_benign	0.1856	benign	-0.334	Destabilizing	0.835	D	0.344	neutral	None	None	None	None	N
T/C	0.9625	likely_pathogenic	0.9006	pathogenic	-0.12	Destabilizing	1.0	D	0.446	neutral	None	None	None	None	N
T/D	0.8856	likely_pathogenic	0.7661	pathogenic	0.234	Stabilizing	0.97	D	0.387	neutral	None	None	None	None	N
T/E	0.8434	likely_pathogenic	0.6742	pathogenic	0.14	Stabilizing	0.97	D	0.394	neutral	None	None	None	None	N
T/F	0.8726	likely_pathogenic	0.6885	pathogenic	-0.988	Destabilizing	0.999	D	0.549	neutral	None	None	None	None	N
T/G	0.5655	likely_pathogenic	0.4651	ambiguous	-0.408	Destabilizing	0.97	D	0.404	neutral	None	None	None	None	N
T/H	0.8295	likely_pathogenic	0.6616	pathogenic	-0.768	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	N
T/I	0.8	likely_pathogenic	0.5721	pathogenic	-0.26	Destabilizing	0.994	D	0.417	neutral	None	None	None	None	N
T/K	0.7247	likely_pathogenic	0.475	ambiguous	-0.161	Destabilizing	0.97	D	0.387	neutral	None	None	None	None	N
T/L	0.5302	ambiguous	0.3409	ambiguous	-0.26	Destabilizing	0.985	D	0.383	neutral	None	None	None	None	N
T/M	0.3139	likely_benign	0.1782	benign	0.046	Stabilizing	1.0	D	0.429	neutral	None	None	None	None	N
T/N	0.4469	ambiguous	0.2945	benign	0.072	Stabilizing	0.961	D	0.363	neutral	None	None	None	None	N
T/P	0.5585	ambiguous	0.4068	ambiguous	-0.26	Destabilizing	0.994	D	0.42	neutral	None	None	None	None	N
T/Q	0.6871	likely_pathogenic	0.4998	ambiguous	-0.182	Destabilizing	0.996	D	0.424	neutral	None	None	None	None	N
T/R	0.7044	likely_pathogenic	0.4135	ambiguous	0.06	Stabilizing	0.996	D	0.435	neutral	None	None	None	None	N
T/S	0.3018	likely_benign	0.2255	benign	-0.132	Destabilizing	0.287	N	0.174	neutral	None	None	None	None	N
T/V	0.6383	likely_pathogenic	0.448	ambiguous	-0.26	Destabilizing	0.985	D	0.351	neutral	None	None	None	None	N
T/W	0.948	likely_pathogenic	0.8524	pathogenic	-1.011	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
T/Y	0.8438	likely_pathogenic	0.6623	pathogenic	-0.706	Destabilizing	0.999	D	0.548	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.