TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18097	54514;54515;54516	chr2:178604800;178604799;178604798	chr2:179469527;179469526;179469525
N2AB	16456	49591;49592;49593	chr2:178604800;178604799;178604798	chr2:179469527;179469526;179469525
N2A	15529	46810;46811;46812	chr2:178604800;178604799;178604798	chr2:179469527;179469526;179469525
N2B	9032	27319;27320;27321	chr2:178604800;178604799;178604798	chr2:179469527;179469526;179469525
Novex-1	9157	27694;27695;27696	chr2:178604800;178604799;178604798	chr2:179469527;179469526;179469525
Novex-2	9224	27895;27896;27897	chr2:178604800;178604799;178604798	chr2:179469527;179469526;179469525
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: Fn3-19
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1314
• 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/T	rs1553681465	None	0.98	N	0.701	0.521	0.720158938049	gnomAD-4.0.0	2.05417E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79998E-06	0	1.65826E-05
I/V	None	None	0.689	N	0.369	0.154	0.567351761699	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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	0.9786	likely_pathogenic	0.9831	pathogenic	-2.422	Highly Destabilizing	0.965	D	0.595	neutral	None	None	None	None	I
I/C	0.9786	likely_pathogenic	0.9825	pathogenic	-1.481	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
I/D	0.9978	likely_pathogenic	0.9984	pathogenic	-2.462	Highly Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	I
I/E	0.9931	likely_pathogenic	0.9945	pathogenic	-2.379	Highly Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	I
I/F	0.8937	likely_pathogenic	0.9244	pathogenic	-1.687	Destabilizing	0.989	D	0.677	prob.neutral	N	0.516965952	None	None	I
I/G	0.9961	likely_pathogenic	0.9967	pathogenic	-2.847	Highly Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	I
I/H	0.9954	likely_pathogenic	0.9969	pathogenic	-2.151	Highly Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
I/K	0.9866	likely_pathogenic	0.9891	pathogenic	-1.835	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	I
I/L	0.2963	likely_benign	0.3293	benign	-1.254	Destabilizing	0.011	N	0.178	neutral	N	0.497802459	None	None	I
I/M	0.4166	ambiguous	0.4803	ambiguous	-0.87	Destabilizing	0.989	D	0.682	prob.neutral	D	0.530857153	None	None	I
I/N	0.9569	likely_pathogenic	0.9658	pathogenic	-1.795	Destabilizing	0.998	D	0.787	deleterious	N	0.520514806	None	None	I
I/P	0.9658	likely_pathogenic	0.9728	pathogenic	-1.619	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	I
I/Q	0.991	likely_pathogenic	0.9934	pathogenic	-1.901	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
I/R	0.9873	likely_pathogenic	0.9894	pathogenic	-1.225	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
I/S	0.9861	likely_pathogenic	0.9885	pathogenic	-2.419	Highly Destabilizing	0.998	D	0.725	prob.delet.	D	0.531110643	None	None	I
I/T	0.9563	likely_pathogenic	0.9661	pathogenic	-2.215	Highly Destabilizing	0.98	D	0.701	prob.neutral	N	0.513170972	None	None	I
I/V	0.1559	likely_benign	0.1589	benign	-1.619	Destabilizing	0.689	D	0.369	neutral	N	0.492895285	None	None	I
I/W	0.9956	likely_pathogenic	0.9975	pathogenic	-1.928	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
I/Y	0.9826	likely_pathogenic	0.9877	pathogenic	-1.715	Destabilizing	0.999	D	0.736	prob.delet.	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.