TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34348	103267;103268;103269	chr2:178533573;178533572;178533571	chr2:179398300;179398299;179398298
N2AB	32707	98344;98345;98346	chr2:178533573;178533572;178533571	chr2:179398300;179398299;179398298
N2A	31780	95563;95564;95565	chr2:178533573;178533572;178533571	chr2:179398300;179398299;179398298
N2B	25283	76072;76073;76074	chr2:178533573;178533572;178533571	chr2:179398300;179398299;179398298
Novex-1	25408	76447;76448;76449	chr2:178533573;178533572;178533571	chr2:179398300;179398299;179398298
Novex-2	25475	76648;76649;76650	chr2:178533573;178533572;178533571	chr2:179398300;179398299;179398298
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-161
• Domain position: 91
• Structural Position: 174
• Q(SASA): 0.0787
• 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
L/P	rs1559027230	None	0.235	D	0.673	0.559	0.768588911288	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.9811	likely_pathogenic	0.9822	pathogenic	-2.992	Highly Destabilizing	0.983	D	0.735	prob.delet.	None	None	None	None	N
L/C	0.9782	likely_pathogenic	0.978	pathogenic	-2.552	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.697	Highly Destabilizing	0.998	D	0.919	deleterious	None	None	None	None	N
L/E	0.9985	likely_pathogenic	0.9987	pathogenic	-3.408	Highly Destabilizing	0.995	D	0.926	deleterious	None	None	None	None	N
L/F	0.8989	likely_pathogenic	0.9015	pathogenic	-1.77	Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
L/G	0.9958	likely_pathogenic	0.9959	pathogenic	-3.593	Highly Destabilizing	0.998	D	0.919	deleterious	None	None	None	None	N
L/H	0.9972	likely_pathogenic	0.9977	pathogenic	-3.153	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/I	0.4064	ambiguous	0.4057	ambiguous	-1.199	Destabilizing	0.991	D	0.635	neutral	None	None	None	None	N
L/K	0.997	likely_pathogenic	0.9974	pathogenic	-2.337	Highly Destabilizing	0.995	D	0.908	deleterious	None	None	None	None	N
L/M	0.5949	likely_pathogenic	0.6009	pathogenic	-1.417	Destabilizing	0.999	D	0.801	deleterious	N	0.510530263	None	None	N
L/N	0.9981	likely_pathogenic	0.9985	pathogenic	-2.946	Highly Destabilizing	0.998	D	0.924	deleterious	None	None	None	None	N
L/P	0.9989	likely_pathogenic	0.9992	pathogenic	-1.786	Destabilizing	0.235	N	0.673	neutral	D	0.540751292	None	None	N
L/Q	0.9952	likely_pathogenic	0.9962	pathogenic	-2.677	Highly Destabilizing	0.997	D	0.924	deleterious	D	0.540751292	None	None	N
L/R	0.9936	likely_pathogenic	0.9946	pathogenic	-2.185	Highly Destabilizing	0.997	D	0.918	deleterious	D	0.529394987	None	None	N
L/S	0.9986	likely_pathogenic	0.9988	pathogenic	-3.595	Highly Destabilizing	0.995	D	0.893	deleterious	None	None	None	None	N
L/T	0.9917	likely_pathogenic	0.9929	pathogenic	-3.146	Highly Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
L/V	0.501	ambiguous	0.506	ambiguous	-1.786	Destabilizing	0.989	D	0.631	neutral	N	0.495177868	None	None	N
L/W	0.9939	likely_pathogenic	0.9946	pathogenic	-2.226	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/Y	0.9901	likely_pathogenic	0.9904	pathogenic	-2.027	Highly Destabilizing	0.999	D	0.876	deleterious	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.