TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18509	55750;55751;55752	chr2:178601472;178601471;178601470	chr2:179466199;179466198;179466197
N2AB	16868	50827;50828;50829	chr2:178601472;178601471;178601470	chr2:179466199;179466198;179466197
N2A	15941	48046;48047;48048	chr2:178601472;178601471;178601470	chr2:179466199;179466198;179466197
N2B	9444	28555;28556;28557	chr2:178601472;178601471;178601470	chr2:179466199;179466198;179466197
Novex-1	9569	28930;28931;28932	chr2:178601472;178601471;178601470	chr2:179466199;179466198;179466197
Novex-2	9636	29131;29132;29133	chr2:178601472;178601471;178601470	chr2:179466199;179466198;179466197
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-22
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3266
• 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
D/V	rs765073012	-0.005	0.997	N	0.747	0.514	0.362160248664	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
D/V	rs765073012	-0.005	0.997	N	0.747	0.514	0.362160248664	gnomAD-4.0.0	4.77897E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.30219E-05	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
D/A	0.6547	likely_pathogenic	0.668	pathogenic	-0.642	Destabilizing	0.978	D	0.658	neutral	N	0.375179893	None	None	I
D/C	0.8644	likely_pathogenic	0.859	pathogenic	-0.25	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
D/E	0.4604	ambiguous	0.4542	ambiguous	-0.751	Destabilizing	0.198	N	0.359	neutral	N	0.403270571	None	None	I
D/F	0.9281	likely_pathogenic	0.9326	pathogenic	-0.292	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
D/G	0.7973	likely_pathogenic	0.8133	pathogenic	-0.988	Destabilizing	0.989	D	0.623	neutral	N	0.414559426	None	None	I
D/H	0.8252	likely_pathogenic	0.8063	pathogenic	-0.665	Destabilizing	1.0	D	0.637	neutral	N	0.494700652	None	None	I
D/I	0.9375	likely_pathogenic	0.9407	pathogenic	0.271	Stabilizing	0.999	D	0.756	deleterious	None	None	None	None	I
D/K	0.9576	likely_pathogenic	0.9564	pathogenic	-0.483	Destabilizing	0.983	D	0.623	neutral	None	None	None	None	I
D/L	0.9152	likely_pathogenic	0.9207	pathogenic	0.271	Stabilizing	0.998	D	0.747	deleterious	None	None	None	None	I
D/M	0.9538	likely_pathogenic	0.9554	pathogenic	0.774	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
D/N	0.4896	ambiguous	0.4829	ambiguous	-0.9	Destabilizing	0.989	D	0.695	prob.neutral	N	0.456566338	None	None	I
D/P	0.9966	likely_pathogenic	0.997	pathogenic	-0.009	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	I
D/Q	0.8695	likely_pathogenic	0.8654	pathogenic	-0.757	Destabilizing	0.995	D	0.671	neutral	None	None	None	None	I
D/R	0.9574	likely_pathogenic	0.958	pathogenic	-0.34	Destabilizing	0.995	D	0.717	prob.delet.	None	None	None	None	I
D/S	0.4762	ambiguous	0.4451	ambiguous	-1.137	Destabilizing	0.983	D	0.618	neutral	None	None	None	None	I
D/T	0.838	likely_pathogenic	0.8382	pathogenic	-0.853	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	I
D/V	0.8333	likely_pathogenic	0.8216	pathogenic	-0.009	Destabilizing	0.997	D	0.747	deleterious	N	0.446792062	None	None	I
D/W	0.9824	likely_pathogenic	0.9837	pathogenic	-0.114	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
D/Y	0.7118	likely_pathogenic	0.6959	pathogenic	-0.064	Destabilizing	1.0	D	0.753	deleterious	N	0.486889245	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.