TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17140	51643;51644;51645	chr2:178610108;178610107;178610106	chr2:179474835;179474834;179474833
N2AB	15499	46720;46721;46722	chr2:178610108;178610107;178610106	chr2:179474835;179474834;179474833
N2A	14572	43939;43940;43941	chr2:178610108;178610107;178610106	chr2:179474835;179474834;179474833
N2B	8075	24448;24449;24450	chr2:178610108;178610107;178610106	chr2:179474835;179474834;179474833
Novex-1	8200	24823;24824;24825	chr2:178610108;178610107;178610106	chr2:179474835;179474834;179474833
Novex-2	8267	25024;25025;25026	chr2:178610108;178610107;178610106	chr2:179474835;179474834;179474833
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: Fn3-12
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.4627
• 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
I/F	None	None	0.808	N	0.499	0.143	0.48300943003	gnomAD-4.0.0	1.59336E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86172E-06	0	0
I/V	rs1457519537	-0.639	0.004	N	0.204	0.047	0.3571064206	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs1457519537	-0.639	0.004	N	0.204	0.047	0.3571064206	gnomAD-4.0.0	1.59336E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-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
I/A	0.5163	ambiguous	0.6497	pathogenic	-1.404	Destabilizing	0.444	N	0.553	neutral	None	None	None	None	N
I/C	0.8692	likely_pathogenic	0.9109	pathogenic	-0.868	Destabilizing	0.992	D	0.709	prob.delet.	None	None	None	None	N
I/D	0.9516	likely_pathogenic	0.9704	pathogenic	-0.775	Destabilizing	0.972	D	0.809	deleterious	None	None	None	None	N
I/E	0.856	likely_pathogenic	0.8973	pathogenic	-0.793	Destabilizing	0.919	D	0.822	deleterious	None	None	None	None	N
I/F	0.3209	likely_benign	0.3959	ambiguous	-0.956	Destabilizing	0.808	D	0.499	neutral	N	0.51199276	None	None	N
I/G	0.9063	likely_pathogenic	0.9512	pathogenic	-1.7	Destabilizing	0.919	D	0.767	deleterious	None	None	None	None	N
I/H	0.8063	likely_pathogenic	0.871	pathogenic	-0.852	Destabilizing	0.992	D	0.837	deleterious	None	None	None	None	N
I/K	0.7109	likely_pathogenic	0.7816	pathogenic	-0.975	Destabilizing	0.919	D	0.809	deleterious	None	None	None	None	N
I/L	0.1537	likely_benign	0.1819	benign	-0.684	Destabilizing	0.002	N	0.19	neutral	N	0.459505069	None	None	N
I/M	0.1528	likely_benign	0.1955	benign	-0.559	Destabilizing	0.808	D	0.603	neutral	N	0.463334808	None	None	N
I/N	0.6592	likely_pathogenic	0.7913	pathogenic	-0.751	Destabilizing	0.963	D	0.837	deleterious	N	0.478073373	None	None	N
I/P	0.8715	likely_pathogenic	0.9036	pathogenic	-0.891	Destabilizing	0.972	D	0.833	deleterious	None	None	None	None	N
I/Q	0.7216	likely_pathogenic	0.8112	pathogenic	-0.939	Destabilizing	0.972	D	0.833	deleterious	None	None	None	None	N
I/R	0.6255	likely_pathogenic	0.6845	pathogenic	-0.357	Destabilizing	0.919	D	0.835	deleterious	None	None	None	None	N
I/S	0.6367	likely_pathogenic	0.7672	pathogenic	-1.341	Destabilizing	0.808	D	0.614	neutral	N	0.500949047	None	None	N
I/T	0.3071	likely_benign	0.4171	ambiguous	-1.242	Destabilizing	0.546	D	0.657	prob.neutral	N	0.437769068	None	None	N
I/V	0.1114	likely_benign	0.1324	benign	-0.891	Destabilizing	0.004	N	0.204	neutral	N	0.444055614	None	None	N
I/W	0.8853	likely_pathogenic	0.9157	pathogenic	-0.989	Destabilizing	0.992	D	0.753	deleterious	None	None	None	None	N
I/Y	0.7829	likely_pathogenic	0.8195	pathogenic	-0.785	Destabilizing	0.919	D	0.681	prob.neutral	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.