TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16846	50761;50762;50763	chr2:178611773;178611772;178611771	chr2:179476500;179476499;179476498
N2AB	15205	45838;45839;45840	chr2:178611773;178611772;178611771	chr2:179476500;179476499;179476498
N2A	14278	43057;43058;43059	chr2:178611773;178611772;178611771	chr2:179476500;179476499;179476498
N2B	7781	23566;23567;23568	chr2:178611773;178611772;178611771	chr2:179476500;179476499;179476498
Novex-1	7906	23941;23942;23943	chr2:178611773;178611772;178611771	chr2:179476500;179476499;179476498
Novex-2	7973	24142;24143;24144	chr2:178611773;178611772;178611771	chr2:179476500;179476499;179476498
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-10
• Domain position: 96
• Structural Position: 130
• Q(SASA): 0.0492
• 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/L	rs1432294105	None	0.041	N	0.517	0.141	0.304435445954	gnomAD-4.0.0	6.84983E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00037E-07	0	0
I/S	rs753344121	-3.271	0.191	N	0.717	0.305	0.613722742674	gnomAD-2.1.1	1.62E-05	None	None	None	None	N	None	0	0	None	0	2.24291E-04	None	0	None	0	0	0
I/S	rs753344121	-3.271	0.191	N	0.717	0.305	0.613722742674	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94628E-04	None	0	0	0	0	0
I/S	rs753344121	-3.271	0.191	N	0.717	0.305	0.613722742674	gnomAD-4.0.0	3.72223E-06	None	None	None	None	N	None	0	0	None	0	8.93895E-05	None	0	0	0	0	3.20636E-05
I/T	rs753344121	-2.967	0.001	N	0.518	0.26	0.524584940466	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	6.5703E-04	None	0	None	0	0	0
I/T	rs753344121	-2.967	0.001	N	0.518	0.26	0.524584940466	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	1.94628E-04	None	0	0	2.94E-05	0	0
I/T	rs753344121	-2.967	0.001	N	0.518	0.26	0.524584940466	gnomAD-4.0.0	7.44446E-06	None	None	None	None	N	None	0	0	None	0	2.23474E-05	None	0	0	5.9372E-06	1.10205E-05	4.80954E-05
I/V	rs1432294105	-1.942	0.003	N	0.208	0.073	0.337621943819	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
I/V	rs1432294105	-1.942	0.003	N	0.208	0.073	0.337621943819	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs1432294105	-1.942	0.003	N	0.208	0.073	0.337621943819	gnomAD-4.0.0	2.48153E-06	None	None	None	None	N	None	2.67415E-05	0	None	0	0	None	0	0	0	2.20381E-05	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	0.8725	likely_pathogenic	0.8759	pathogenic	-2.592	Highly Destabilizing	0.115	N	0.661	prob.neutral	None	None	None	None	N
I/C	0.9664	likely_pathogenic	0.9622	pathogenic	-2.626	Highly Destabilizing	0.944	D	0.706	prob.delet.	None	None	None	None	N
I/D	0.9984	likely_pathogenic	0.9986	pathogenic	-3.133	Highly Destabilizing	0.687	D	0.795	deleterious	None	None	None	None	N
I/E	0.9942	likely_pathogenic	0.9952	pathogenic	-2.988	Highly Destabilizing	0.687	D	0.771	deleterious	None	None	None	None	N
I/F	0.7115	likely_pathogenic	0.7168	pathogenic	-1.658	Destabilizing	0.771	D	0.7	prob.delet.	D	0.538508634	None	None	N
I/G	0.9919	likely_pathogenic	0.9929	pathogenic	-3.03	Highly Destabilizing	0.687	D	0.735	deleterious	None	None	None	None	N
I/H	0.9946	likely_pathogenic	0.9951	pathogenic	-2.175	Highly Destabilizing	0.981	D	0.801	deleterious	None	None	None	None	N
I/K	0.9892	likely_pathogenic	0.9918	pathogenic	-2.057	Highly Destabilizing	0.687	D	0.771	deleterious	None	None	None	None	N
I/L	0.386	ambiguous	0.393	ambiguous	-1.361	Destabilizing	0.041	N	0.517	neutral	N	0.461966749	None	None	N
I/M	0.3914	ambiguous	0.3944	ambiguous	-1.696	Destabilizing	0.771	D	0.664	prob.neutral	N	0.473644101	None	None	N
I/N	0.9814	likely_pathogenic	0.9828	pathogenic	-2.325	Highly Destabilizing	0.624	D	0.808	deleterious	N	0.51264135	None	None	N
I/P	0.9738	likely_pathogenic	0.9742	pathogenic	-1.751	Destabilizing	0.817	D	0.807	deleterious	None	None	None	None	N
I/Q	0.9899	likely_pathogenic	0.9916	pathogenic	-2.371	Highly Destabilizing	0.817	D	0.797	deleterious	None	None	None	None	N
I/R	0.9809	likely_pathogenic	0.9859	pathogenic	-1.569	Destabilizing	0.687	D	0.798	deleterious	None	None	None	None	N
I/S	0.9495	likely_pathogenic	0.9546	pathogenic	-2.981	Highly Destabilizing	0.191	N	0.717	prob.delet.	N	0.463728274	None	None	N
I/T	0.7846	likely_pathogenic	0.7852	pathogenic	-2.704	Highly Destabilizing	0.001	N	0.518	neutral	N	0.466977191	None	None	N
I/V	0.0955	likely_benign	0.094	benign	-1.751	Destabilizing	0.003	N	0.208	neutral	N	0.470816905	None	None	N
I/W	0.9926	likely_pathogenic	0.993	pathogenic	-1.835	Destabilizing	0.981	D	0.783	deleterious	None	None	None	None	N
I/Y	0.9823	likely_pathogenic	0.983	pathogenic	-1.626	Destabilizing	0.817	D	0.715	prob.delet.	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.