TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5719	17380;17381;17382	chr2:178731720;178731719;178731718	chr2:179596447;179596446;179596445
N2AB	5402	16429;16430;16431	chr2:178731720;178731719;178731718	chr2:179596447;179596446;179596445
N2A	4475	13648;13649;13650	chr2:178731720;178731719;178731718	chr2:179596447;179596446;179596445
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-40
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.4192
• Predicted PPI site: I

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
I/M	None	None	0.033	N	0.409	0.06	0.369495900351	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/T	rs769635185	-0.779	None	N	0.159	0.115	0.292062946507	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
I/T	rs769635185	-0.779	None	N	0.159	0.115	0.292062946507	gnomAD-4.0.0	8.21832E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.08043E-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
I/A	0.0893	likely_benign	0.0892	benign	-1.331	Destabilizing	None	N	0.163	neutral	None	None	None	None	I
I/C	0.3473	ambiguous	0.3449	ambiguous	-0.816	Destabilizing	0.245	N	0.423	neutral	None	None	None	None	I
I/D	0.2357	likely_benign	0.2097	benign	-0.258	Destabilizing	0.004	N	0.324	neutral	None	None	None	None	I
I/E	0.2217	likely_benign	0.197	benign	-0.259	Destabilizing	None	N	0.325	neutral	None	None	None	None	I
I/F	0.0862	likely_benign	0.0846	benign	-0.853	Destabilizing	0.033	N	0.358	neutral	N	0.440282669	None	None	I
I/G	0.2007	likely_benign	0.2026	benign	-1.632	Destabilizing	0.004	N	0.322	neutral	None	None	None	None	I
I/H	0.1794	likely_benign	0.1663	benign	-0.686	Destabilizing	0.497	N	0.478	neutral	None	None	None	None	I
I/K	0.1642	likely_benign	0.1428	benign	-0.688	Destabilizing	0.008	N	0.313	neutral	None	None	None	None	I
I/L	0.0744	likely_benign	0.074	benign	-0.594	Destabilizing	None	N	0.095	neutral	N	0.415058937	None	None	I
I/M	0.0785	likely_benign	0.0778	benign	-0.535	Destabilizing	0.033	N	0.409	neutral	N	0.449075511	None	None	I
I/N	0.0812	likely_benign	0.077	benign	-0.513	Destabilizing	0.014	N	0.362	neutral	N	0.423870422	None	None	I
I/P	0.3638	ambiguous	0.3852	ambiguous	-0.807	Destabilizing	0.037	N	0.403	neutral	None	None	None	None	I
I/Q	0.1684	likely_benign	0.1555	benign	-0.66	Destabilizing	0.018	N	0.428	neutral	None	None	None	None	I
I/R	0.122	likely_benign	0.1083	benign	-0.148	Destabilizing	0.018	N	0.402	neutral	None	None	None	None	I
I/S	0.0684	likely_benign	0.066	benign	-1.199	Destabilizing	None	N	0.209	neutral	N	0.34465749	None	None	I
I/T	0.0609	likely_benign	0.0585	benign	-1.075	Destabilizing	None	N	0.159	neutral	N	0.36760892	None	None	I
I/V	0.0611	likely_benign	0.0618	benign	-0.807	Destabilizing	None	N	0.1	neutral	N	0.406978172	None	None	I
I/W	0.4896	ambiguous	0.4711	ambiguous	-0.862	Destabilizing	0.497	N	0.449	neutral	None	None	None	None	I
I/Y	0.226	likely_benign	0.2134	benign	-0.639	Destabilizing	0.085	N	0.448	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.