TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30751	92476;92477;92478	chr2:178549375;178549374;178549373	chr2:179414102;179414101;179414100
N2AB	29110	87553;87554;87555	chr2:178549375;178549374;178549373	chr2:179414102;179414101;179414100
N2A	28183	84772;84773;84774	chr2:178549375;178549374;178549373	chr2:179414102;179414101;179414100
N2B	21686	65281;65282;65283	chr2:178549375;178549374;178549373	chr2:179414102;179414101;179414100
Novex-1	21811	65656;65657;65658	chr2:178549375;178549374;178549373	chr2:179414102;179414101;179414100
Novex-2	21878	65857;65858;65859	chr2:178549375;178549374;178549373	chr2:179414102;179414101;179414100
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: Fn3-112
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.168
• 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/M	None	None	1.0	D	0.832	0.428	0.614131634805	gnomAD-4.0.0	1.59125E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8582E-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	0.9815	likely_pathogenic	0.9808	pathogenic	-2.599	Highly Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	I
I/C	0.9824	likely_pathogenic	0.9837	pathogenic	-1.923	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
I/D	0.998	likely_pathogenic	0.9977	pathogenic	-2.816	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
I/E	0.9944	likely_pathogenic	0.9929	pathogenic	-2.69	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
I/F	0.8637	likely_pathogenic	0.86	pathogenic	-1.676	Destabilizing	1.0	D	0.849	deleterious	D	0.547743186	None	None	I
I/G	0.9955	likely_pathogenic	0.9951	pathogenic	-3.064	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	I
I/H	0.9949	likely_pathogenic	0.9941	pathogenic	-2.357	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
I/K	0.9864	likely_pathogenic	0.983	pathogenic	-2.021	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
I/L	0.4281	ambiguous	0.45	ambiguous	-1.292	Destabilizing	0.993	D	0.437	neutral	N	0.485187988	None	None	I
I/M	0.5623	ambiguous	0.5583	ambiguous	-1.149	Destabilizing	1.0	D	0.832	deleterious	D	0.556861447	None	None	I
I/N	0.9662	likely_pathogenic	0.9554	pathogenic	-2.103	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.56923171	None	None	I
I/P	0.9639	likely_pathogenic	0.9588	pathogenic	-1.705	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	I
I/Q	0.9912	likely_pathogenic	0.9892	pathogenic	-2.151	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
I/R	0.9845	likely_pathogenic	0.9815	pathogenic	-1.483	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
I/S	0.9812	likely_pathogenic	0.9798	pathogenic	-2.766	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.550531571	None	None	I
I/T	0.9642	likely_pathogenic	0.9656	pathogenic	-2.511	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.539010681	None	None	I
I/V	0.1807	likely_benign	0.2182	benign	-1.705	Destabilizing	0.993	D	0.405	neutral	N	0.471412146	None	None	I
I/W	0.9954	likely_pathogenic	0.9956	pathogenic	-1.946	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
I/Y	0.9773	likely_pathogenic	0.9742	pathogenic	-1.736	Destabilizing	1.0	D	0.876	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.