TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21305	64138;64139;64140	chr2:178587298;178587297;178587296	chr2:179452025;179452024;179452023
N2AB	19664	59215;59216;59217	chr2:178587298;178587297;178587296	chr2:179452025;179452024;179452023
N2A	18737	56434;56435;56436	chr2:178587298;178587297;178587296	chr2:179452025;179452024;179452023
N2B	12240	36943;36944;36945	chr2:178587298;178587297;178587296	chr2:179452025;179452024;179452023
Novex-1	12365	37318;37319;37320	chr2:178587298;178587297;178587296	chr2:179452025;179452024;179452023
Novex-2	12432	37519;37520;37521	chr2:178587298;178587297;178587296	chr2:179452025;179452024;179452023
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-42
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2299
• 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/N	None	None	0.946	N	0.809	0.328	0.239901079897	gnomAD-4.0.0	1.59279E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86035E-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	0.9483	likely_pathogenic	0.9493	pathogenic	-1.349	Destabilizing	0.87	D	0.686	prob.neutral	None	None	None	None	N
K/C	0.8814	likely_pathogenic	0.8834	pathogenic	-1.272	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
K/D	0.9942	likely_pathogenic	0.9949	pathogenic	-1.674	Destabilizing	0.959	D	0.827	deleterious	None	None	None	None	N
K/E	0.8995	likely_pathogenic	0.891	pathogenic	-1.349	Destabilizing	0.716	D	0.683	prob.neutral	N	0.510882204	None	None	N
K/F	0.9666	likely_pathogenic	0.9684	pathogenic	-0.74	Destabilizing	0.994	D	0.844	deleterious	None	None	None	None	N
K/G	0.9654	likely_pathogenic	0.9677	pathogenic	-1.841	Destabilizing	0.959	D	0.777	deleterious	None	None	None	None	N
K/H	0.7558	likely_pathogenic	0.7422	pathogenic	-1.586	Destabilizing	0.994	D	0.833	deleterious	None	None	None	None	N
K/I	0.826	likely_pathogenic	0.8162	pathogenic	0.058	Stabilizing	0.973	D	0.854	deleterious	N	0.519806953	None	None	N
K/L	0.7851	likely_pathogenic	0.7823	pathogenic	0.058	Stabilizing	0.959	D	0.777	deleterious	None	None	None	None	N
K/M	0.5946	likely_pathogenic	0.6014	pathogenic	-0.309	Destabilizing	0.998	D	0.828	deleterious	None	None	None	None	N
K/N	0.97	likely_pathogenic	0.9717	pathogenic	-1.591	Destabilizing	0.946	D	0.809	deleterious	N	0.499525899	None	None	N
K/P	0.9987	likely_pathogenic	0.9989	pathogenic	-0.392	Destabilizing	0.979	D	0.841	deleterious	None	None	None	None	N
K/Q	0.5273	ambiguous	0.4951	ambiguous	-1.196	Destabilizing	0.946	D	0.813	deleterious	N	0.484548742	None	None	N
K/R	0.1377	likely_benign	0.1345	benign	-0.54	Destabilizing	0.035	N	0.388	neutral	N	0.494372578	None	None	N
K/S	0.9642	likely_pathogenic	0.9633	pathogenic	-2.162	Highly Destabilizing	0.87	D	0.721	prob.delet.	None	None	None	None	N
K/T	0.8456	likely_pathogenic	0.8361	pathogenic	-1.558	Destabilizing	0.946	D	0.787	deleterious	N	0.477685434	None	None	N
K/V	0.8005	likely_pathogenic	0.7959	pathogenic	-0.392	Destabilizing	0.959	D	0.819	deleterious	None	None	None	None	N
K/W	0.9517	likely_pathogenic	0.9546	pathogenic	-0.742	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
K/Y	0.8957	likely_pathogenic	0.898	pathogenic	-0.378	Destabilizing	0.979	D	0.854	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.