TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21949	66070;66071;66072	chr2:178582958;178582957;178582956	chr2:179447685;179447684;179447683
N2AB	20308	61147;61148;61149	chr2:178582958;178582957;178582956	chr2:179447685;179447684;179447683
N2A	19381	58366;58367;58368	chr2:178582958;178582957;178582956	chr2:179447685;179447684;179447683
N2B	12884	38875;38876;38877	chr2:178582958;178582957;178582956	chr2:179447685;179447684;179447683
Novex-1	13009	39250;39251;39252	chr2:178582958;178582957;178582956	chr2:179447685;179447684;179447683
Novex-2	13076	39451;39452;39453	chr2:178582958;178582957;178582956	chr2:179447685;179447684;179447683
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-125
• Domain position: 84
• Structural Position: 172
• Q(SASA): 0.0577
• 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/V	rs779413774	-1.383	0.333	N	0.177	0.085	0.418718287753	gnomAD-2.1.1	4.72E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.9E-06	0
I/V	rs779413774	-1.383	0.333	N	0.177	0.085	0.418718287753	gnomAD-4.0.0	3.61153E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.41457E-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	0.8992	likely_pathogenic	0.8654	pathogenic	-2.687	Highly Destabilizing	0.992	D	0.595	neutral	None	None	None	None	N
I/C	0.9168	likely_pathogenic	0.889	pathogenic	-2.316	Highly Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
I/D	0.999	likely_pathogenic	0.9985	pathogenic	-2.539	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
I/E	0.9957	likely_pathogenic	0.9944	pathogenic	-2.314	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
I/F	0.5289	ambiguous	0.5095	ambiguous	-1.656	Destabilizing	0.998	D	0.643	neutral	N	0.485575028	None	None	N
I/G	0.9878	likely_pathogenic	0.9826	pathogenic	-3.255	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
I/H	0.9926	likely_pathogenic	0.9884	pathogenic	-2.607	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
I/K	0.9887	likely_pathogenic	0.9832	pathogenic	-1.978	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
I/L	0.2745	likely_benign	0.277	benign	-1.044	Destabilizing	0.889	D	0.427	neutral	N	0.48872719	None	None	N
I/M	0.2827	likely_benign	0.2604	benign	-1.156	Destabilizing	0.998	D	0.643	neutral	N	0.517514089	None	None	N
I/N	0.9842	likely_pathogenic	0.9752	pathogenic	-2.267	Highly Destabilizing	0.999	D	0.819	deleterious	N	0.494090255	None	None	N
I/P	0.9963	likely_pathogenic	0.9945	pathogenic	-1.572	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
I/Q	0.9882	likely_pathogenic	0.9824	pathogenic	-2.128	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
I/R	0.9805	likely_pathogenic	0.9706	pathogenic	-1.727	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
I/S	0.9704	likely_pathogenic	0.9561	pathogenic	-3.106	Highly Destabilizing	0.998	D	0.739	prob.delet.	N	0.497234817	None	None	N
I/T	0.9606	likely_pathogenic	0.9447	pathogenic	-2.716	Highly Destabilizing	0.989	D	0.695	prob.neutral	N	0.490692847	None	None	N
I/V	0.1064	likely_benign	0.1056	benign	-1.572	Destabilizing	0.333	N	0.177	neutral	N	0.451729027	None	None	N
I/W	0.9846	likely_pathogenic	0.9795	pathogenic	-1.91	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
I/Y	0.9492	likely_pathogenic	0.9364	pathogenic	-1.681	Destabilizing	1.0	D	0.723	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.