TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18708	56347;56348;56349	chr2:178599779;178599778;178599777	chr2:179464506;179464505;179464504
N2AB	17067	51424;51425;51426	chr2:178599779;178599778;178599777	chr2:179464506;179464505;179464504
N2A	16140	48643;48644;48645	chr2:178599779;178599778;178599777	chr2:179464506;179464505;179464504
N2B	9643	29152;29153;29154	chr2:178599779;178599778;178599777	chr2:179464506;179464505;179464504
Novex-1	9768	29527;29528;29529	chr2:178599779;178599778;178599777	chr2:179464506;179464505;179464504
Novex-2	9835	29728;29729;29730	chr2:178599779;178599778;178599777	chr2:179464506;179464505;179464504
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: Ig-116
• Domain position: 21
• Structural Position: 35
• Q(SASA): 0.3316
• 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	None	None	0.505	N	0.661	0.517	0.685061634186	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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	0.9278	likely_pathogenic	0.9095	pathogenic	-2.234	Highly Destabilizing	0.218	N	0.614	neutral	None	None	None	None	I
I/C	0.9147	likely_pathogenic	0.9053	pathogenic	-1.387	Destabilizing	0.973	D	0.684	prob.neutral	None	None	None	None	I
I/D	0.9974	likely_pathogenic	0.9962	pathogenic	-2.122	Highly Destabilizing	0.906	D	0.797	deleterious	None	None	None	None	I
I/E	0.9898	likely_pathogenic	0.9861	pathogenic	-1.968	Destabilizing	0.906	D	0.785	deleterious	None	None	None	None	I
I/F	0.5038	ambiguous	0.4359	ambiguous	-1.352	Destabilizing	0.782	D	0.618	neutral	N	0.491197066	None	None	I
I/G	0.9794	likely_pathogenic	0.9698	pathogenic	-2.716	Highly Destabilizing	0.906	D	0.763	deleterious	None	None	None	None	I
I/H	0.9871	likely_pathogenic	0.9823	pathogenic	-2.012	Highly Destabilizing	0.991	D	0.802	deleterious	None	None	None	None	I
I/K	0.9827	likely_pathogenic	0.9762	pathogenic	-1.699	Destabilizing	0.906	D	0.785	deleterious	None	None	None	None	I
I/L	0.2541	likely_benign	0.2341	benign	-0.885	Destabilizing	0.084	N	0.387	neutral	N	0.517266159	None	None	I
I/M	0.2499	likely_benign	0.2289	benign	-0.691	Destabilizing	0.782	D	0.611	neutral	N	0.510400992	None	None	I
I/N	0.9609	likely_pathogenic	0.948	pathogenic	-1.805	Destabilizing	0.957	D	0.804	deleterious	D	0.522264277	None	None	I
I/P	0.9896	likely_pathogenic	0.986	pathogenic	-1.31	Destabilizing	0.967	D	0.799	deleterious	None	None	None	None	I
I/Q	0.9824	likely_pathogenic	0.9774	pathogenic	-1.781	Destabilizing	0.967	D	0.798	deleterious	None	None	None	None	I
I/R	0.9769	likely_pathogenic	0.969	pathogenic	-1.283	Destabilizing	0.906	D	0.803	deleterious	None	None	None	None	I
I/S	0.9541	likely_pathogenic	0.9409	pathogenic	-2.493	Highly Destabilizing	0.782	D	0.755	deleterious	N	0.506897237	None	None	I
I/T	0.9109	likely_pathogenic	0.8978	pathogenic	-2.199	Highly Destabilizing	0.505	D	0.661	neutral	N	0.51447657	None	None	I
I/V	0.1088	likely_benign	0.0985	benign	-1.31	Destabilizing	None	N	0.256	neutral	N	0.41574401	None	None	I
I/W	0.9737	likely_pathogenic	0.9684	pathogenic	-1.633	Destabilizing	0.991	D	0.814	deleterious	None	None	None	None	I
I/Y	0.9126	likely_pathogenic	0.8807	pathogenic	-1.353	Destabilizing	0.906	D	0.699	prob.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.