TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28114	84565;84566;84567	chr2:178561792;178561791;178561790	chr2:179426519;179426518;179426517
N2AB	26473	79642;79643;79644	chr2:178561792;178561791;178561790	chr2:179426519;179426518;179426517
N2A	25546	76861;76862;76863	chr2:178561792;178561791;178561790	chr2:179426519;179426518;179426517
N2B	19049	57370;57371;57372	chr2:178561792;178561791;178561790	chr2:179426519;179426518;179426517
Novex-1	19174	57745;57746;57747	chr2:178561792;178561791;178561790	chr2:179426519;179426518;179426517
Novex-2	19241	57946;57947;57948	chr2:178561792;178561791;178561790	chr2:179426519;179426518;179426517
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: Fn3-92
• Domain position: 60
• Structural Position: 91
• Q(SASA): 0.1672
• 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
I/V	rs1703767853	None	0.426	N	0.475	0.11	0.404034981753	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
I/V	rs1703767853	None	0.426	N	0.475	0.11	0.404034981753	gnomAD-4.0.0	3.09873E-06	None	None	None	None	I	None	0	1.66728E-05	None	0	0	None	1.56255E-05	0	2.5429E-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
I/A	0.6901	likely_pathogenic	0.6508	pathogenic	-1.734	Destabilizing	0.033	N	0.369	neutral	None	None	None	None	I
I/C	0.77	likely_pathogenic	0.7422	pathogenic	-1.289	Destabilizing	0.997	D	0.641	neutral	None	None	None	None	I
I/D	0.9812	likely_pathogenic	0.9725	pathogenic	-0.84	Destabilizing	0.987	D	0.762	deleterious	None	None	None	None	I
I/E	0.9462	likely_pathogenic	0.9256	pathogenic	-0.691	Destabilizing	0.975	D	0.745	deleterious	None	None	None	None	I
I/F	0.1934	likely_benign	0.2125	benign	-0.911	Destabilizing	0.983	D	0.497	neutral	N	0.402385137	None	None	I
I/G	0.9184	likely_pathogenic	0.9061	pathogenic	-2.183	Highly Destabilizing	0.95	D	0.678	prob.neutral	None	None	None	None	I
I/H	0.8738	likely_pathogenic	0.848	pathogenic	-1.282	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
I/K	0.8607	likely_pathogenic	0.8145	pathogenic	-1.161	Destabilizing	0.975	D	0.749	deleterious	None	None	None	None	I
I/L	0.1064	likely_benign	0.1104	benign	-0.507	Destabilizing	0.63	D	0.477	neutral	N	0.427184794	None	None	I
I/M	0.0935	likely_benign	0.1013	benign	-0.592	Destabilizing	0.994	D	0.505	neutral	N	0.475421458	None	None	I
I/N	0.7706	likely_pathogenic	0.7255	pathogenic	-1.347	Destabilizing	0.983	D	0.803	deleterious	N	0.501349551	None	None	I
I/P	0.9831	likely_pathogenic	0.9789	pathogenic	-0.889	Destabilizing	0.987	D	0.793	deleterious	None	None	None	None	I
I/Q	0.828	likely_pathogenic	0.7973	pathogenic	-1.244	Destabilizing	0.987	D	0.813	deleterious	None	None	None	None	I
I/R	0.7919	likely_pathogenic	0.7413	pathogenic	-0.873	Destabilizing	0.987	D	0.797	deleterious	None	None	None	None	I
I/S	0.7061	likely_pathogenic	0.6814	pathogenic	-2.133	Highly Destabilizing	0.805	D	0.571	neutral	N	0.474344526	None	None	I
I/T	0.6537	likely_pathogenic	0.6165	pathogenic	-1.828	Destabilizing	0.892	D	0.521	neutral	N	0.484675659	None	None	I
I/V	0.111	likely_benign	0.1074	benign	-0.889	Destabilizing	0.426	N	0.475	neutral	N	0.444151615	None	None	I
I/W	0.8811	likely_pathogenic	0.8705	pathogenic	-1.058	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
I/Y	0.6627	likely_pathogenic	0.6422	pathogenic	-0.786	Destabilizing	0.996	D	0.648	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.