TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24410	73453;73454;73455	chr2:178572904;178572903;178572902	chr2:179437631;179437630;179437629
N2AB	22769	68530;68531;68532	chr2:178572904;178572903;178572902	chr2:179437631;179437630;179437629
N2A	21842	65749;65750;65751	chr2:178572904;178572903;178572902	chr2:179437631;179437630;179437629
N2B	15345	46258;46259;46260	chr2:178572904;178572903;178572902	chr2:179437631;179437630;179437629
Novex-1	15470	46633;46634;46635	chr2:178572904;178572903;178572902	chr2:179437631;179437630;179437629
Novex-2	15537	46834;46835;46836	chr2:178572904;178572903;178572902	chr2:179437631;179437630;179437629
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-65
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.1952
• 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
P/L	rs368510432	None	0.993	N	0.774	0.472	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs368510432	None	0.993	N	0.774	0.472	None	gnomAD-4.0.0	2.56358E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78822E-06	0	0
P/S	None	None	0.987	N	0.698	0.351	0.231231049324	gnomAD-4.0.0	1.5922E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85958E-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
P/A	0.09	likely_benign	0.0877	benign	-1.45	Destabilizing	0.117	N	0.453	neutral	N	0.463484156	None	None	I
P/C	0.623	likely_pathogenic	0.637	pathogenic	-0.698	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
P/D	0.8076	likely_pathogenic	0.8028	pathogenic	-1.407	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	I
P/E	0.5763	likely_pathogenic	0.5767	pathogenic	-1.374	Destabilizing	0.995	D	0.754	deleterious	None	None	None	None	I
P/F	0.7089	likely_pathogenic	0.7289	pathogenic	-1.033	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	I
P/G	0.4802	ambiguous	0.4816	ambiguous	-1.787	Destabilizing	0.966	D	0.694	prob.neutral	None	None	None	None	I
P/H	0.4531	ambiguous	0.4722	ambiguous	-1.373	Destabilizing	1.0	D	0.849	deleterious	N	0.486085089	None	None	I
P/I	0.6281	likely_pathogenic	0.6216	pathogenic	-0.609	Destabilizing	0.995	D	0.861	deleterious	None	None	None	None	I
P/K	0.6657	likely_pathogenic	0.6569	pathogenic	-1.199	Destabilizing	0.995	D	0.767	deleterious	None	None	None	None	I
P/L	0.3508	ambiguous	0.3136	benign	-0.609	Destabilizing	0.993	D	0.774	deleterious	N	0.511542724	None	None	I
P/M	0.533	ambiguous	0.5371	ambiguous	-0.399	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
P/N	0.6817	likely_pathogenic	0.7056	pathogenic	-1.002	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	I
P/Q	0.4446	ambiguous	0.4527	ambiguous	-1.132	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	I
P/R	0.5497	ambiguous	0.5331	ambiguous	-0.712	Destabilizing	0.997	D	0.841	deleterious	N	0.519558121	None	None	I
P/S	0.2418	likely_benign	0.2584	benign	-1.484	Destabilizing	0.987	D	0.698	prob.neutral	N	0.496173947	None	None	I
P/T	0.2733	likely_benign	0.2773	benign	-1.348	Destabilizing	0.993	D	0.724	prob.delet.	N	0.50466987	None	None	I
P/V	0.4275	ambiguous	0.4218	ambiguous	-0.856	Destabilizing	0.99	D	0.723	prob.delet.	None	None	None	None	I
P/W	0.8498	likely_pathogenic	0.8562	pathogenic	-1.309	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
P/Y	0.6883	likely_pathogenic	0.7042	pathogenic	-0.989	Destabilizing	1.0	D	0.886	deleterious	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.