TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21734	65425;65426;65427	chr2:178584351;178584350;178584349	chr2:179449078;179449077;179449076
N2AB	20093	60502;60503;60504	chr2:178584351;178584350;178584349	chr2:179449078;179449077;179449076
N2A	19166	57721;57722;57723	chr2:178584351;178584350;178584349	chr2:179449078;179449077;179449076
N2B	12669	38230;38231;38232	chr2:178584351;178584350;178584349	chr2:179449078;179449077;179449076
Novex-1	12794	38605;38606;38607	chr2:178584351;178584350;178584349	chr2:179449078;179449077;179449076
Novex-2	12861	38806;38807;38808	chr2:178584351;178584350;178584349	chr2:179449078;179449077;179449076
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: Fn3-45
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0588
• 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
I/M	rs765344234	-2.035	0.994	N	0.616	0.378	0.492267288202	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
I/M	rs765344234	-2.035	0.994	N	0.616	0.378	0.492267288202	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/M	rs765344234	-2.035	0.994	N	0.616	0.378	0.492267288202	gnomAD-4.0.0	2.4807E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39288E-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
I/A	0.9067	likely_pathogenic	0.8364	pathogenic	-2.99	Highly Destabilizing	0.931	D	0.539	neutral	None	None	None	None	N
I/C	0.9148	likely_pathogenic	0.8767	pathogenic	-1.907	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
I/D	0.9987	likely_pathogenic	0.9978	pathogenic	-3.497	Highly Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
I/E	0.9969	likely_pathogenic	0.9955	pathogenic	-3.172	Highly Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
I/F	0.7843	likely_pathogenic	0.7509	pathogenic	-1.719	Destabilizing	0.994	D	0.612	neutral	N	0.493176931	None	None	N
I/G	0.9899	likely_pathogenic	0.9812	pathogenic	-3.589	Highly Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
I/H	0.9965	likely_pathogenic	0.9942	pathogenic	-3.172	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
I/K	0.9948	likely_pathogenic	0.9928	pathogenic	-2.114	Highly Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
I/L	0.4401	ambiguous	0.3761	ambiguous	-1.171	Destabilizing	0.689	D	0.305	neutral	N	0.483080936	None	None	N
I/M	0.4779	ambiguous	0.4028	ambiguous	-1.329	Destabilizing	0.994	D	0.616	neutral	N	0.507846095	None	None	N
I/N	0.9719	likely_pathogenic	0.9597	pathogenic	-2.815	Highly Destabilizing	0.998	D	0.812	deleterious	N	0.4939374	None	None	N
I/P	0.9922	likely_pathogenic	0.9873	pathogenic	-1.771	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
I/Q	0.9946	likely_pathogenic	0.9921	pathogenic	-2.461	Highly Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
I/R	0.9922	likely_pathogenic	0.9891	pathogenic	-2.164	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
I/S	0.9542	likely_pathogenic	0.9275	pathogenic	-3.347	Highly Destabilizing	0.994	D	0.698	prob.neutral	N	0.482581095	None	None	N
I/T	0.8841	likely_pathogenic	0.8318	pathogenic	-2.863	Highly Destabilizing	0.961	D	0.45	neutral	N	0.475579656	None	None	N
I/V	0.1275	likely_benign	0.1025	benign	-1.771	Destabilizing	0.044	N	0.183	neutral	N	0.320347251	None	None	N
I/W	0.9978	likely_pathogenic	0.997	pathogenic	-2.057	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
I/Y	0.981	likely_pathogenic	0.9776	pathogenic	-1.922	Destabilizing	0.999	D	0.617	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.