TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8245	24958;24959;24960	chr2:178718373;178718372;178718371	chr2:179583100;179583099;179583098
N2AB	7928	24007;24008;24009	chr2:178718373;178718372;178718371	chr2:179583100;179583099;179583098
N2A	7001	21226;21227;21228	chr2:178718373;178718372;178718371	chr2:179583100;179583099;179583098
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-67
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0387
• 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/M	None	None	0.927	N	0.661	0.39	0.484109215787	gnomAD-4.0.0	1.5914E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	None	0	0	0	0	0
I/T	rs1309374626	-2.695	0.425	N	0.657	0.368	0.605748623547	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/T	rs1309374626	-2.695	0.425	N	0.657	0.368	0.605748623547	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8586E-06	0	0
I/V	None	None	0.002	N	0.257	0.113	0.301789629655	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5287	ambiguous	0.5278	ambiguous	-3.02	Highly Destabilizing	0.013	N	0.451	neutral	None	None	None	None	N
I/C	0.9539	likely_pathogenic	0.9462	pathogenic	-2.294	Highly Destabilizing	0.981	D	0.771	deleterious	None	None	None	None	N
I/D	0.9986	likely_pathogenic	0.9981	pathogenic	-3.573	Highly Destabilizing	0.704	D	0.776	deleterious	None	None	None	None	N
I/E	0.9929	likely_pathogenic	0.9917	pathogenic	-3.292	Highly Destabilizing	0.543	D	0.751	deleterious	None	None	None	None	N
I/F	0.8462	likely_pathogenic	0.8043	pathogenic	-1.612	Destabilizing	0.704	D	0.685	prob.neutral	None	None	None	None	N
I/G	0.9723	likely_pathogenic	0.966	pathogenic	-3.563	Highly Destabilizing	0.704	D	0.73	prob.delet.	None	None	None	None	N
I/H	0.9965	likely_pathogenic	0.9954	pathogenic	-3.011	Highly Destabilizing	0.944	D	0.825	deleterious	None	None	None	None	N
I/K	0.9901	likely_pathogenic	0.988	pathogenic	-2.196	Highly Destabilizing	0.473	N	0.755	deleterious	N	0.513079883	None	None	N
I/L	0.2611	likely_benign	0.234	benign	-1.388	Destabilizing	0.139	N	0.403	neutral	N	0.495733307	None	None	N
I/M	0.293	likely_benign	0.2797	benign	-1.655	Destabilizing	0.927	D	0.661	neutral	N	0.501558993	None	None	N
I/N	0.9818	likely_pathogenic	0.9784	pathogenic	-2.763	Highly Destabilizing	0.944	D	0.807	deleterious	None	None	None	None	N
I/P	0.9918	likely_pathogenic	0.9897	pathogenic	-1.924	Destabilizing	0.944	D	0.806	deleterious	None	None	None	None	N
I/Q	0.9878	likely_pathogenic	0.9851	pathogenic	-2.494	Highly Destabilizing	0.085	N	0.6	neutral	None	None	None	None	N
I/R	0.9798	likely_pathogenic	0.9766	pathogenic	-2.057	Highly Destabilizing	0.863	D	0.804	deleterious	N	0.513333372	None	None	N
I/S	0.8893	likely_pathogenic	0.8865	pathogenic	-3.328	Highly Destabilizing	0.543	D	0.714	prob.delet.	None	None	None	None	N
I/T	0.5385	ambiguous	0.5292	ambiguous	-2.91	Highly Destabilizing	0.425	N	0.657	neutral	N	0.501052014	None	None	N
I/V	0.0899	likely_benign	0.0839	benign	-1.924	Destabilizing	0.002	N	0.257	neutral	N	0.422230052	None	None	N
I/W	0.9972	likely_pathogenic	0.9957	pathogenic	-1.998	Destabilizing	0.017	N	0.602	neutral	None	None	None	None	N
I/Y	0.991	likely_pathogenic	0.9884	pathogenic	-1.883	Destabilizing	0.893	D	0.753	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.