TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27846	83761;83762;83763	chr2:178562596;178562595;178562594	chr2:179427323;179427322;179427321
N2AB	26205	78838;78839;78840	chr2:178562596;178562595;178562594	chr2:179427323;179427322;179427321
N2A	25278	76057;76058;76059	chr2:178562596;178562595;178562594	chr2:179427323;179427322;179427321
N2B	18781	56566;56567;56568	chr2:178562596;178562595;178562594	chr2:179427323;179427322;179427321
Novex-1	18906	56941;56942;56943	chr2:178562596;178562595;178562594	chr2:179427323;179427322;179427321
Novex-2	18973	57142;57143;57144	chr2:178562596;178562595;178562594	chr2:179427323;179427322;179427321
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-90
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.7708
• 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
Y/C	None	None	0.976	N	0.549	0.297	0.475272412942	gnomAD-4.0.0	1.37125E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80047E-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
Y/A	0.8443	likely_pathogenic	0.8812	pathogenic	-0.686	Destabilizing	0.118	N	0.551	neutral	None	None	None	None	I
Y/C	0.3515	ambiguous	0.4181	ambiguous	0.091	Stabilizing	0.976	D	0.549	neutral	N	0.468557628	None	None	I
Y/D	0.8821	likely_pathogenic	0.9121	pathogenic	0.972	Stabilizing	0.777	D	0.568	neutral	N	0.485772829	None	None	I
Y/E	0.952	likely_pathogenic	0.9629	pathogenic	0.948	Stabilizing	0.393	N	0.571	neutral	None	None	None	None	I
Y/F	0.0881	likely_benign	0.1072	benign	-0.397	Destabilizing	None	N	0.305	neutral	N	0.460260004	None	None	I
Y/G	0.8661	likely_pathogenic	0.8913	pathogenic	-0.866	Destabilizing	0.568	D	0.591	neutral	None	None	None	None	I
Y/H	0.4622	ambiguous	0.5484	ambiguous	0.207	Stabilizing	0.001	N	0.315	neutral	N	0.474367298	None	None	I
Y/I	0.6193	likely_pathogenic	0.6697	pathogenic	-0.241	Destabilizing	0.005	N	0.479	neutral	None	None	None	None	I
Y/K	0.9479	likely_pathogenic	0.9555	pathogenic	0.257	Stabilizing	0.073	N	0.567	neutral	None	None	None	None	I
Y/L	0.6324	likely_pathogenic	0.6801	pathogenic	-0.241	Destabilizing	None	N	0.224	neutral	None	None	None	None	I
Y/M	0.7337	likely_pathogenic	0.7875	pathogenic	-0.063	Destabilizing	0.406	N	0.513	neutral	None	None	None	None	I
Y/N	0.4766	ambiguous	0.5383	ambiguous	0.087	Stabilizing	0.632	D	0.579	neutral	N	0.519209521	None	None	I
Y/P	0.9911	likely_pathogenic	0.9931	pathogenic	-0.369	Destabilizing	0.934	D	0.555	neutral	None	None	None	None	I
Y/Q	0.8994	likely_pathogenic	0.9229	pathogenic	0.108	Stabilizing	0.406	N	0.529	neutral	None	None	None	None	I
Y/R	0.9119	likely_pathogenic	0.9243	pathogenic	0.539	Stabilizing	0.485	N	0.579	neutral	None	None	None	None	I
Y/S	0.7461	likely_pathogenic	0.7997	pathogenic	-0.378	Destabilizing	0.329	N	0.587	neutral	N	0.470657541	None	None	I
Y/T	0.8661	likely_pathogenic	0.9005	pathogenic	-0.31	Destabilizing	0.393	N	0.553	neutral	None	None	None	None	I
Y/V	0.5833	likely_pathogenic	0.6244	pathogenic	-0.369	Destabilizing	0.002	N	0.249	neutral	None	None	None	None	I
Y/W	0.6067	likely_pathogenic	0.6729	pathogenic	-0.515	Destabilizing	0.887	D	0.443	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.