TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24452	73579;73580;73581	chr2:178572778;178572777;178572776	chr2:179437505;179437504;179437503
N2AB	22811	68656;68657;68658	chr2:178572778;178572777;178572776	chr2:179437505;179437504;179437503
N2A	21884	65875;65876;65877	chr2:178572778;178572777;178572776	chr2:179437505;179437504;179437503
N2B	15387	46384;46385;46386	chr2:178572778;178572777;178572776	chr2:179437505;179437504;179437503
Novex-1	15512	46759;46760;46761	chr2:178572778;178572777;178572776	chr2:179437505;179437504;179437503
Novex-2	15579	46960;46961;46962	chr2:178572778;178572777;178572776	chr2:179437505;179437504;179437503
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: Ig-132
• Domain position: 22
• Structural Position: 35
• Q(SASA): 0.325
• 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	rs1708703348	None	0.011	N	0.229	0.082	0.312001716656	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.9224	likely_pathogenic	0.9302	pathogenic	-1.819	Destabilizing	0.845	D	0.569	neutral	None	None	None	None	I
I/C	0.9388	likely_pathogenic	0.9407	pathogenic	-1.295	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	I
I/D	0.9988	likely_pathogenic	0.9988	pathogenic	-0.928	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	I
I/E	0.9946	likely_pathogenic	0.9946	pathogenic	-0.866	Destabilizing	0.987	D	0.761	deleterious	None	None	None	None	I
I/F	0.3621	ambiguous	0.3487	ambiguous	-1.111	Destabilizing	0.967	D	0.616	neutral	N	0.500085908	None	None	I
I/G	0.9892	likely_pathogenic	0.9907	pathogenic	-2.209	Highly Destabilizing	0.987	D	0.761	deleterious	None	None	None	None	I
I/H	0.9876	likely_pathogenic	0.9864	pathogenic	-1.344	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	I
I/K	0.9873	likely_pathogenic	0.9872	pathogenic	-1.262	Destabilizing	0.987	D	0.761	deleterious	None	None	None	None	I
I/L	0.2403	likely_benign	0.2493	benign	-0.794	Destabilizing	0.426	N	0.483	neutral	N	0.495877908	None	None	I
I/M	0.2699	likely_benign	0.2817	benign	-0.733	Destabilizing	0.983	D	0.605	neutral	N	0.502171786	None	None	I
I/N	0.9815	likely_pathogenic	0.9824	pathogenic	-1.169	Destabilizing	0.994	D	0.769	deleterious	D	0.532139325	None	None	I
I/P	0.9948	likely_pathogenic	0.9945	pathogenic	-1.105	Destabilizing	0.996	D	0.768	deleterious	None	None	None	None	I
I/Q	0.9827	likely_pathogenic	0.9823	pathogenic	-1.241	Destabilizing	0.996	D	0.78	deleterious	None	None	None	None	I
I/R	0.9804	likely_pathogenic	0.9785	pathogenic	-0.765	Destabilizing	0.987	D	0.773	deleterious	None	None	None	None	I
I/S	0.9579	likely_pathogenic	0.9616	pathogenic	-1.918	Destabilizing	0.983	D	0.691	prob.neutral	N	0.502260691	None	None	I
I/T	0.9372	likely_pathogenic	0.9416	pathogenic	-1.719	Destabilizing	0.892	D	0.621	neutral	N	0.503866852	None	None	I
I/V	0.0928	likely_benign	0.103	benign	-1.105	Destabilizing	0.011	N	0.229	neutral	N	0.437023359	None	None	I
I/W	0.9769	likely_pathogenic	0.9734	pathogenic	-1.185	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
I/Y	0.913	likely_pathogenic	0.9021	pathogenic	-0.968	Destabilizing	0.987	D	0.628	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.