TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17773	53542;53543;53544	chr2:178607285;178607284;178607283	chr2:179472012;179472011;179472010
N2AB	16132	48619;48620;48621	chr2:178607285;178607284;178607283	chr2:179472012;179472011;179472010
N2A	15205	45838;45839;45840	chr2:178607285;178607284;178607283	chr2:179472012;179472011;179472010
N2B	8708	26347;26348;26349	chr2:178607285;178607284;178607283	chr2:179472012;179472011;179472010
Novex-1	8833	26722;26723;26724	chr2:178607285;178607284;178607283	chr2:179472012;179472011;179472010
Novex-2	8900	26923;26924;26925	chr2:178607285;178607284;178607283	chr2:179472012;179472011;179472010
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: Fn3-17
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2177
• 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
P/A	None	None	0.996	N	0.58	0.349	0.235038932564	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.1657	likely_benign	0.1951	benign	-1.444	Destabilizing	0.996	D	0.58	neutral	N	0.441263238	None	None	N
P/C	0.8135	likely_pathogenic	0.8503	pathogenic	-1.139	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/D	0.9601	likely_pathogenic	0.9664	pathogenic	-1.238	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
P/E	0.8727	likely_pathogenic	0.887	pathogenic	-1.202	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
P/F	0.9424	likely_pathogenic	0.9569	pathogenic	-0.997	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
P/G	0.7883	likely_pathogenic	0.8201	pathogenic	-1.791	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
P/H	0.8329	likely_pathogenic	0.8369	pathogenic	-1.179	Destabilizing	1.0	D	0.789	deleterious	N	0.488481182	None	None	N
P/I	0.6143	likely_pathogenic	0.7016	pathogenic	-0.581	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
P/K	0.9153	likely_pathogenic	0.9344	pathogenic	-1.333	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
P/L	0.4018	ambiguous	0.477	ambiguous	-0.581	Destabilizing	0.999	D	0.743	deleterious	N	0.439839086	None	None	N
P/M	0.6752	likely_pathogenic	0.7484	pathogenic	-0.568	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/N	0.8989	likely_pathogenic	0.908	pathogenic	-1.241	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
P/Q	0.7668	likely_pathogenic	0.7792	pathogenic	-1.331	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/R	0.8598	likely_pathogenic	0.8742	pathogenic	-0.828	Destabilizing	0.999	D	0.765	deleterious	N	0.463069764	None	None	N
P/S	0.5712	likely_pathogenic	0.5897	pathogenic	-1.786	Destabilizing	0.998	D	0.698	prob.neutral	N	0.477282753	None	None	N
P/T	0.2935	likely_benign	0.3522	ambiguous	-1.621	Destabilizing	0.884	D	0.36	neutral	N	0.443516896	None	None	N
P/V	0.3866	ambiguous	0.4702	ambiguous	-0.834	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
P/W	0.9766	likely_pathogenic	0.9801	pathogenic	-1.189	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
P/Y	0.9359	likely_pathogenic	0.9409	pathogenic	-0.897	Destabilizing	1.0	D	0.823	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.