TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33300	100123;100124;100125	chr2:178537211;178537210;178537209	chr2:179401938;179401937;179401936
N2AB	31659	95200;95201;95202	chr2:178537211;178537210;178537209	chr2:179401938;179401937;179401936
N2A	30732	92419;92420;92421	chr2:178537211;178537210;178537209	chr2:179401938;179401937;179401936
N2B	24235	72928;72929;72930	chr2:178537211;178537210;178537209	chr2:179401938;179401937;179401936
Novex-1	24360	73303;73304;73305	chr2:178537211;178537210;178537209	chr2:179401938;179401937;179401936
Novex-2	24427	73504;73505;73506	chr2:178537211;178537210;178537209	chr2:179401938;179401937;179401936
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: Fn3-130
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.3044
• 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/V	None	None	0.002	N	0.161	0.067	0.428401797576	gnomAD-4.0.0	1.37193E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16214E-05	1.66019E-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	0.5756	likely_pathogenic	0.5236	ambiguous	-1.664	Destabilizing	0.029	N	0.231	neutral	None	None	None	None	I
I/C	0.8784	likely_pathogenic	0.8482	pathogenic	-1.171	Destabilizing	0.998	D	0.541	neutral	None	None	None	None	I
I/D	0.974	likely_pathogenic	0.9618	pathogenic	-1.045	Destabilizing	0.974	D	0.635	neutral	None	None	None	None	I
I/E	0.9036	likely_pathogenic	0.8906	pathogenic	-0.992	Destabilizing	0.974	D	0.618	neutral	None	None	None	None	I
I/F	0.3751	ambiguous	0.2899	benign	-1.003	Destabilizing	0.966	D	0.526	neutral	N	0.427664796	None	None	I
I/G	0.9391	likely_pathogenic	0.9179	pathogenic	-2.033	Highly Destabilizing	0.842	D	0.59	neutral	None	None	None	None	I
I/H	0.9385	likely_pathogenic	0.9121	pathogenic	-1.099	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	I
I/K	0.8689	likely_pathogenic	0.8448	pathogenic	-1.222	Destabilizing	0.974	D	0.621	neutral	None	None	None	None	I
I/L	0.2267	likely_benign	0.1748	benign	-0.706	Destabilizing	0.267	N	0.312	neutral	N	0.436897568	None	None	I
I/M	0.1866	likely_benign	0.1573	benign	-0.668	Destabilizing	0.986	D	0.525	neutral	N	0.495332583	None	None	I
I/N	0.8514	likely_pathogenic	0.8086	pathogenic	-1.185	Destabilizing	0.989	D	0.635	neutral	D	0.522345826	None	None	I
I/P	0.8471	likely_pathogenic	0.8326	pathogenic	-0.995	Destabilizing	0.974	D	0.641	neutral	None	None	None	None	I
I/Q	0.8492	likely_pathogenic	0.831	pathogenic	-1.267	Destabilizing	0.991	D	0.645	neutral	None	None	None	None	I
I/R	0.8186	likely_pathogenic	0.7853	pathogenic	-0.67	Destabilizing	0.974	D	0.635	neutral	None	None	None	None	I
I/S	0.7391	likely_pathogenic	0.7027	pathogenic	-1.846	Destabilizing	0.669	D	0.552	neutral	N	0.502623915	None	None	I
I/T	0.3507	ambiguous	0.3056	benign	-1.659	Destabilizing	0.801	D	0.519	neutral	N	0.498756891	None	None	I
I/V	0.1013	likely_benign	0.0861	benign	-0.995	Destabilizing	0.002	N	0.161	neutral	N	0.406803948	None	None	I
I/W	0.9249	likely_pathogenic	0.8875	pathogenic	-1.089	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	I
I/Y	0.8612	likely_pathogenic	0.8116	pathogenic	-0.866	Destabilizing	0.991	D	0.567	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.