TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5380	16363;16364;16365	chr2:178733038;178733037;178733036	chr2:179597765;179597764;179597763
N2AB	5063	15412;15413;15414	chr2:178733038;178733037;178733036	chr2:179597765;179597764;179597763
N2A	4136	12631;12632;12633	chr2:178733038;178733037;178733036	chr2:179597765;179597764;179597763
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: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-37
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1213
• 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/T	rs767107151	-2.374	0.896	N	0.727	0.498	0.695068833554	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	0	0	None	0	2.80426E-04	None	0	None	0	0	0
I/T	rs767107151	-2.374	0.896	N	0.727	0.498	0.695068833554	gnomAD-4.0.0	7.96105E-06	None	None	None	None	N	None	0	0	None	0	1.11247E-04	None	0	0	2.8592E-06	0	0
I/V	rs1280725528	None	0.004	N	0.233	0.112	0.348983352498	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85923E-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	0.6271	likely_pathogenic	0.6655	pathogenic	-2.15	Highly Destabilizing	0.702	D	0.706	prob.neutral	None	None	None	None	N
I/C	0.9379	likely_pathogenic	0.9465	pathogenic	-1.213	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
I/D	0.9963	likely_pathogenic	0.9961	pathogenic	-2.178	Highly Destabilizing	0.996	D	0.854	deleterious	None	None	None	None	N
I/E	0.9901	likely_pathogenic	0.9902	pathogenic	-1.901	Destabilizing	0.988	D	0.845	deleterious	None	None	None	None	N
I/F	0.4363	ambiguous	0.412	ambiguous	-1.189	Destabilizing	0.968	D	0.771	deleterious	N	0.504126291	None	None	N
I/G	0.9596	likely_pathogenic	0.962	pathogenic	-2.731	Highly Destabilizing	0.988	D	0.826	deleterious	None	None	None	None	N
I/H	0.9881	likely_pathogenic	0.9881	pathogenic	-2.346	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
I/K	0.9866	likely_pathogenic	0.9862	pathogenic	-1.235	Destabilizing	0.988	D	0.848	deleterious	None	None	None	None	N
I/L	0.1834	likely_benign	0.1875	benign	-0.447	Destabilizing	0.437	N	0.389	neutral	N	0.46797349	None	None	N
I/M	0.1756	likely_benign	0.1815	benign	-0.484	Destabilizing	0.984	D	0.732	prob.delet.	N	0.499538439	None	None	N
I/N	0.9529	likely_pathogenic	0.9545	pathogenic	-1.681	Destabilizing	0.995	D	0.855	deleterious	N	0.517985089	None	None	N
I/P	0.9804	likely_pathogenic	0.9795	pathogenic	-0.998	Destabilizing	0.996	D	0.854	deleterious	None	None	None	None	N
I/Q	0.9831	likely_pathogenic	0.9838	pathogenic	-1.413	Destabilizing	0.996	D	0.849	deleterious	None	None	None	None	N
I/R	0.9767	likely_pathogenic	0.976	pathogenic	-1.302	Destabilizing	0.988	D	0.854	deleterious	None	None	None	None	N
I/S	0.8771	likely_pathogenic	0.8894	pathogenic	-2.393	Highly Destabilizing	0.984	D	0.813	deleterious	D	0.528715304	None	None	N
I/T	0.6172	likely_pathogenic	0.6403	pathogenic	-1.958	Destabilizing	0.896	D	0.727	prob.delet.	N	0.50747324	None	None	N
I/V	0.088	likely_benign	0.0865	benign	-0.998	Destabilizing	0.004	N	0.233	neutral	N	0.423286058	None	None	N
I/W	0.9822	likely_pathogenic	0.9818	pathogenic	-1.577	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
I/Y	0.9237	likely_pathogenic	0.9153	pathogenic	-1.249	Destabilizing	0.988	D	0.805	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.