TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4706	14341;14342;14343	chr2:178738337;178738336;178738335	chr2:179603064;179603063;179603062
N2AB	4389	13390;13391;13392	chr2:178738337;178738336;178738335	chr2:179603064;179603063;179603062
N2A	3462	10609;10610;10611	chr2:178738337;178738336;178738335	chr2:179603064;179603063;179603062
N2B	4343	13252;13253;13254	chr2:178738337;178738336;178738335	chr2:179603064;179603063;179603062
Novex-1	4468	13627;13628;13629	chr2:178738337;178738336;178738335	chr2:179603064;179603063;179603062
Novex-2	4535	13828;13829;13830	chr2:178738337;178738336;178738335	chr2:179603064;179603063;179603062
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-30
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2553
• 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	rs267599072	None	0.987	N	0.439	0.232	0.141422826196	gnomAD-4.0.0	4.10836E-06	None	None	None	None	I	None	2.98954E-05	0	None	0	0	None	0	0	4.50005E-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	0.6494	likely_pathogenic	0.6958	pathogenic	-2.276	Highly Destabilizing	0.919	D	0.42	neutral	None	None	None	None	I
I/C	0.9616	likely_pathogenic	0.9664	pathogenic	-1.489	Destabilizing	0.999	D	0.518	neutral	None	None	None	None	I
I/D	0.9927	likely_pathogenic	0.9927	pathogenic	-2.219	Highly Destabilizing	0.996	D	0.665	neutral	None	None	None	None	I
I/E	0.9772	likely_pathogenic	0.9781	pathogenic	-2.081	Highly Destabilizing	0.996	D	0.661	neutral	None	None	None	None	I
I/F	0.6292	likely_pathogenic	0.6594	pathogenic	-1.392	Destabilizing	0.968	D	0.433	neutral	N	0.468584502	None	None	I
I/G	0.9541	likely_pathogenic	0.9575	pathogenic	-2.751	Highly Destabilizing	0.996	D	0.657	neutral	None	None	None	None	I
I/H	0.9875	likely_pathogenic	0.988	pathogenic	-2.096	Highly Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
I/K	0.9684	likely_pathogenic	0.9671	pathogenic	-1.587	Destabilizing	0.988	D	0.659	neutral	None	None	None	None	I
I/L	0.147	likely_benign	0.1477	benign	-0.951	Destabilizing	0.011	N	0.113	neutral	N	0.424210734	None	None	I
I/M	0.1309	likely_benign	0.1338	benign	-0.825	Destabilizing	0.987	D	0.439	neutral	N	0.452113851	None	None	I
I/N	0.9144	likely_pathogenic	0.9205	pathogenic	-1.66	Destabilizing	0.995	D	0.679	prob.neutral	N	0.479391945	None	None	I
I/P	0.7512	likely_pathogenic	0.7934	pathogenic	-1.369	Destabilizing	0.996	D	0.682	prob.neutral	None	None	None	None	I
I/Q	0.9636	likely_pathogenic	0.9659	pathogenic	-1.67	Destabilizing	0.996	D	0.672	neutral	None	None	None	None	I
I/R	0.9513	likely_pathogenic	0.9511	pathogenic	-1.176	Destabilizing	0.988	D	0.68	prob.neutral	None	None	None	None	I
I/S	0.8649	likely_pathogenic	0.8812	pathogenic	-2.36	Highly Destabilizing	0.984	D	0.545	neutral	N	0.470161011	None	None	I
I/T	0.6235	likely_pathogenic	0.6795	pathogenic	-2.09	Highly Destabilizing	0.946	D	0.477	neutral	N	0.442956343	None	None	I
I/V	0.1687	likely_benign	0.2	benign	-1.369	Destabilizing	0.437	N	0.364	neutral	N	0.446037953	None	None	I
I/W	0.9823	likely_pathogenic	0.981	pathogenic	-1.675	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
I/Y	0.9616	likely_pathogenic	0.9573	pathogenic	-1.407	Destabilizing	0.988	D	0.508	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.