TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5972	18139;18140;18141	chr2:178730619;178730618;178730617	chr2:179595346;179595345;179595344
N2AB	5655	17188;17189;17190	chr2:178730619;178730618;178730617	chr2:179595346;179595345;179595344
N2A	4728	14407;14408;14409	chr2:178730619;178730618;178730617	chr2:179595346;179595345;179595344
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-43
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.3834
• 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
N/S	rs1447713863	None	0.999	N	0.637	0.289	0.374255764437	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs1447713863	None	0.999	N	0.637	0.289	0.374255764437	gnomAD-4.0.0	3.04486E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61475E-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
N/A	0.7783	likely_pathogenic	0.8268	pathogenic	-0.879	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
N/C	0.7701	likely_pathogenic	0.8047	pathogenic	0.016	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
N/D	0.4169	ambiguous	0.495	ambiguous	-0.625	Destabilizing	0.999	D	0.662	neutral	D	0.531056602	None	None	N
N/E	0.8911	likely_pathogenic	0.9156	pathogenic	-0.487	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
N/F	0.9368	likely_pathogenic	0.9555	pathogenic	-0.546	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
N/G	0.6104	likely_pathogenic	0.6716	pathogenic	-1.261	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	N
N/H	0.3211	likely_benign	0.3867	ambiguous	-0.975	Destabilizing	1.0	D	0.7	prob.neutral	N	0.49916591	None	None	N
N/I	0.8903	likely_pathogenic	0.9087	pathogenic	0.111	Stabilizing	1.0	D	0.771	deleterious	D	0.52887996	None	None	N
N/K	0.8168	likely_pathogenic	0.8553	pathogenic	-0.279	Destabilizing	1.0	D	0.717	prob.delet.	N	0.488730976	None	None	N
N/L	0.7986	likely_pathogenic	0.8295	pathogenic	0.111	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
N/M	0.8477	likely_pathogenic	0.8716	pathogenic	0.501	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
N/P	0.9661	likely_pathogenic	0.97	pathogenic	-0.188	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
N/Q	0.7904	likely_pathogenic	0.8208	pathogenic	-0.819	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
N/R	0.7832	likely_pathogenic	0.8206	pathogenic	-0.433	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
N/S	0.1836	likely_benign	0.2291	benign	-0.989	Destabilizing	0.999	D	0.637	neutral	N	0.51964753	None	None	N
N/T	0.5582	ambiguous	0.6292	pathogenic	-0.643	Destabilizing	0.999	D	0.702	prob.neutral	N	0.491657492	None	None	N
N/V	0.8803	likely_pathogenic	0.902	pathogenic	-0.188	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
N/W	0.9766	likely_pathogenic	0.9806	pathogenic	-0.34	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
N/Y	0.5803	likely_pathogenic	0.6759	pathogenic	-0.113	Destabilizing	1.0	D	0.75	deleterious	N	0.50871179	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.