TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1591	4996;4997;4998	chr2:178777192;178777191;178777190	chr2:179641919;179641918;179641917
N2AB	1591	4996;4997;4998	chr2:178777192;178777191;178777190	chr2:179641919;179641918;179641917
N2A	1591	4996;4997;4998	chr2:178777192;178777191;178777190	chr2:179641919;179641918;179641917
N2B	1545	4858;4859;4860	chr2:178777192;178777191;178777190	chr2:179641919;179641918;179641917
Novex-1	1545	4858;4859;4860	chr2:178777192;178777191;178777190	chr2:179641919;179641918;179641917
Novex-2	1545	4858;4859;4860	chr2:178777192;178777191;178777190	chr2:179641919;179641918;179641917
Novex-3	1591	4996;4997;4998	chr2:178777192;178777191;178777190	chr2:179641919;179641918;179641917

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-7
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1209
• 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
K/R	rs1308021841	None	0.999	N	0.638	0.437	0.30212335484	gnomAD-4.0.0	1.59064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8568E-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
K/A	0.9876	likely_pathogenic	0.9839	pathogenic	-1.391	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
K/C	0.9654	likely_pathogenic	0.9456	pathogenic	-1.523	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
K/D	0.9988	likely_pathogenic	0.9982	pathogenic	-1.783	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
K/E	0.9816	likely_pathogenic	0.968	pathogenic	-1.487	Destabilizing	0.999	D	0.607	neutral	D	0.675490667	None	None	N
K/F	0.9951	likely_pathogenic	0.9917	pathogenic	-0.783	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
K/G	0.9939	likely_pathogenic	0.9926	pathogenic	-1.896	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/H	0.8616	likely_pathogenic	0.7902	pathogenic	-2.028	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/I	0.9736	likely_pathogenic	0.9582	pathogenic	0.035	Stabilizing	1.0	D	0.855	deleterious	D	0.672318291	None	None	N
K/L	0.9328	likely_pathogenic	0.9057	pathogenic	0.035	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/M	0.913	likely_pathogenic	0.8782	pathogenic	-0.194	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
K/N	0.9931	likely_pathogenic	0.9887	pathogenic	-1.797	Destabilizing	1.0	D	0.713	prob.delet.	D	0.65222586	None	None	N
K/P	0.9993	likely_pathogenic	0.9991	pathogenic	-0.418	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/Q	0.8037	likely_pathogenic	0.7016	pathogenic	-1.451	Destabilizing	1.0	D	0.703	prob.neutral	D	0.673964937	None	None	N
K/R	0.1796	likely_benign	0.1464	benign	-1.068	Destabilizing	0.999	D	0.638	neutral	N	0.474031792	None	None	N
K/S	0.9939	likely_pathogenic	0.9915	pathogenic	-2.378	Highly Destabilizing	0.999	D	0.616	neutral	None	None	None	None	N
K/T	0.9856	likely_pathogenic	0.9827	pathogenic	-1.804	Destabilizing	1.0	D	0.773	deleterious	D	0.57714035	None	None	N
K/V	0.9597	likely_pathogenic	0.9431	pathogenic	-0.418	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
K/W	0.9877	likely_pathogenic	0.9794	pathogenic	-0.822	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
K/Y	0.9763	likely_pathogenic	0.9617	pathogenic	-0.457	Destabilizing	1.0	D	0.834	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.