TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16957	51094;51095;51096	chr2:178611260;178611259;178611258	chr2:179475987;179475986;179475985
N2AB	15316	46171;46172;46173	chr2:178611260;178611259;178611258	chr2:179475987;179475986;179475985
N2A	14389	43390;43391;43392	chr2:178611260;178611259;178611258	chr2:179475987;179475986;179475985
N2B	7892	23899;23900;23901	chr2:178611260;178611259;178611258	chr2:179475987;179475986;179475985
Novex-1	8017	24274;24275;24276	chr2:178611260;178611259;178611258	chr2:179475987;179475986;179475985
Novex-2	8084	24475;24476;24477	chr2:178611260;178611259;178611258	chr2:179475987;179475986;179475985
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: Ig-111
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1652
• 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/F	rs372013419	-1.583	0.934	N	0.704	0.251	0.463328977263	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
I/F	rs372013419	-1.583	0.934	N	0.704	0.251	0.463328977263	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/F	rs372013419	-1.583	0.934	N	0.704	0.251	0.463328977263	gnomAD-4.0.0	1.24066E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.69616E-06	0	0
I/N	rs368450275	-1.759	0.989	D	0.845	0.675	0.803589953288	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
I/T	rs368450275	-2.236	0.801	D	0.707	0.542	None	gnomAD-2.1.1	2.84E-05	None	None	None	None	I	None	0	0	None	9.98E-05	0	None	0	None	0	5.37E-05	0
I/T	rs368450275	-2.236	0.801	D	0.707	0.542	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/T	rs368450275	-2.236	0.801	D	0.707	0.542	None	gnomAD-4.0.0	9.92491E-06	None	None	None	None	I	None	0	0	None	3.38203E-05	2.24346E-05	None	7.8235E-05	0	6.78448E-06	1.10006E-05	0
I/V	rs372013419	-1.385	0.005	N	0.246	0.118	None	gnomAD-2.1.1	1.62E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.67E-05	1.79E-05	1.67336E-04
I/V	rs372013419	-1.385	0.005	N	0.246	0.118	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs372013419	-1.385	0.005	N	0.246	0.118	None	gnomAD-4.0.0	1.79895E-05	None	None	None	None	I	None	1.33636E-05	0	None	0	0	None	1.5647E-05	1.64799E-04	2.03539E-05	1.10028E-05	1.60364E-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
I/A	0.4845	ambiguous	0.453	ambiguous	-2.205	Highly Destabilizing	0.525	D	0.662	neutral	None	None	None	None	I
I/C	0.8608	likely_pathogenic	0.8764	pathogenic	-1.503	Destabilizing	0.998	D	0.758	deleterious	None	None	None	None	I
I/D	0.9891	likely_pathogenic	0.9842	pathogenic	-1.973	Destabilizing	0.991	D	0.845	deleterious	None	None	None	None	I
I/E	0.9688	likely_pathogenic	0.9601	pathogenic	-1.849	Destabilizing	0.974	D	0.827	deleterious	None	None	None	None	I
I/F	0.292	likely_benign	0.2912	benign	-1.34	Destabilizing	0.934	D	0.704	prob.neutral	N	0.488154198	None	None	I
I/G	0.9254	likely_pathogenic	0.916	pathogenic	-2.666	Highly Destabilizing	0.974	D	0.819	deleterious	None	None	None	None	I
I/H	0.9603	likely_pathogenic	0.9543	pathogenic	-1.958	Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	I
I/K	0.933	likely_pathogenic	0.9147	pathogenic	-1.767	Destabilizing	0.974	D	0.819	deleterious	None	None	None	None	I
I/L	0.1363	likely_benign	0.1398	benign	-0.936	Destabilizing	0.002	N	0.265	neutral	N	0.477970219	None	None	I
I/M	0.1158	likely_benign	0.1173	benign	-0.8	Destabilizing	0.934	D	0.691	prob.neutral	D	0.522440731	None	None	I
I/N	0.9103	likely_pathogenic	0.8924	pathogenic	-1.8	Destabilizing	0.989	D	0.845	deleterious	D	0.645584952	None	None	I
I/P	0.9316	likely_pathogenic	0.9195	pathogenic	-1.333	Destabilizing	0.991	D	0.845	deleterious	None	None	None	None	I
I/Q	0.9431	likely_pathogenic	0.9328	pathogenic	-1.807	Destabilizing	0.991	D	0.844	deleterious	None	None	None	None	I
I/R	0.9019	likely_pathogenic	0.8784	pathogenic	-1.315	Destabilizing	0.974	D	0.845	deleterious	None	None	None	None	I
I/S	0.7783	likely_pathogenic	0.7458	pathogenic	-2.482	Highly Destabilizing	0.891	D	0.805	deleterious	D	0.524915379	None	None	I
I/T	0.4464	ambiguous	0.5293	ambiguous	-2.219	Highly Destabilizing	0.801	D	0.707	prob.neutral	D	0.604451383	None	None	I
I/V	0.0766	likely_benign	0.0803	benign	-1.333	Destabilizing	0.005	N	0.246	neutral	N	0.516799116	None	None	I
I/W	0.9414	likely_pathogenic	0.9355	pathogenic	-1.565	Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	I
I/Y	0.8597	likely_pathogenic	0.8439	pathogenic	-1.317	Destabilizing	0.974	D	0.776	deleterious	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.