TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21691	65296;65297;65298	chr2:178584480;178584479;178584478	chr2:179449207;179449206;179449205
N2AB	20050	60373;60374;60375	chr2:178584480;178584479;178584478	chr2:179449207;179449206;179449205
N2A	19123	57592;57593;57594	chr2:178584480;178584479;178584478	chr2:179449207;179449206;179449205
N2B	12626	38101;38102;38103	chr2:178584480;178584479;178584478	chr2:179449207;179449206;179449205
Novex-1	12751	38476;38477;38478	chr2:178584480;178584479;178584478	chr2:179449207;179449206;179449205
Novex-2	12818	38677;38678;38679	chr2:178584480;178584479;178584478	chr2:179449207;179449206;179449205
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: Fn3-45
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2021
• 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/N	None	-1.782	0.998	D	0.839	0.519	0.86998522814	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/N	None	-1.782	0.998	D	0.839	0.519	0.86998522814	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/N	None	-1.782	0.998	D	0.839	0.519	0.86998522814	gnomAD-4.0.0	5.5791E-06	None	None	None	None	I	None	0	1.66789E-05	None	0	0	None	0	0	6.78235E-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	0.9268	likely_pathogenic	0.9301	pathogenic	-2.353	Highly Destabilizing	0.985	D	0.677	prob.neutral	None	None	None	None	I
I/C	0.9474	likely_pathogenic	0.9433	pathogenic	-1.471	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
I/D	0.9941	likely_pathogenic	0.9942	pathogenic	-2.239	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	I
I/E	0.9859	likely_pathogenic	0.9875	pathogenic	-2.107	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	I
I/F	0.8582	likely_pathogenic	0.8528	pathogenic	-1.534	Destabilizing	0.989	D	0.695	prob.neutral	D	0.52322015	None	None	I
I/G	0.9873	likely_pathogenic	0.9873	pathogenic	-2.819	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
I/H	0.9894	likely_pathogenic	0.9882	pathogenic	-2.158	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
I/K	0.9793	likely_pathogenic	0.9797	pathogenic	-1.703	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	I
I/L	0.2597	likely_benign	0.2367	benign	-1.056	Destabilizing	0.031	N	0.19	neutral	N	0.511539761	None	None	I
I/M	0.4739	ambiguous	0.4483	ambiguous	-0.804	Destabilizing	0.989	D	0.685	prob.neutral	D	0.525755045	None	None	I
I/N	0.9228	likely_pathogenic	0.9116	pathogenic	-1.762	Destabilizing	0.998	D	0.839	deleterious	D	0.526769003	None	None	I
I/P	0.9153	likely_pathogenic	0.9399	pathogenic	-1.464	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	I
I/Q	0.981	likely_pathogenic	0.9818	pathogenic	-1.782	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	I
I/R	0.9716	likely_pathogenic	0.9728	pathogenic	-1.232	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	I
I/S	0.9542	likely_pathogenic	0.9531	pathogenic	-2.459	Highly Destabilizing	0.998	D	0.797	deleterious	D	0.526008534	None	None	I
I/T	0.9196	likely_pathogenic	0.9089	pathogenic	-2.196	Highly Destabilizing	0.98	D	0.754	deleterious	N	0.503131339	None	None	I
I/V	0.079	likely_benign	0.0761	benign	-1.464	Destabilizing	0.689	D	0.417	neutral	N	0.47296273	None	None	I
I/W	0.9956	likely_pathogenic	0.9951	pathogenic	-1.818	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
I/Y	0.9751	likely_pathogenic	0.9767	pathogenic	-1.557	Destabilizing	0.999	D	0.761	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.