TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5006	15241;15242;15243	chr2:178734908;178734907;178734906	chr2:179599635;179599634;179599633
N2AB	4689	14290;14291;14292	chr2:178734908;178734907;178734906	chr2:179599635;179599634;179599633
N2A	3762	11509;11510;11511	chr2:178734908;178734907;178734906	chr2:179599635;179599634;179599633
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-33
• Domain position: 26
• Structural Position: 38
• Q(SASA): 0.675
• Predicted PPI site: I

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	None	None	0.999	N	0.537	0.336	0.362361684037	gnomAD-4.0.0	1.36915E-06	None	None	None	None	I	None	2.98829E-05	0	None	0	0	None	0	0	8.99753E-07	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	0.5894	likely_pathogenic	0.7048	pathogenic	-0.088	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	I
K/C	0.8639	likely_pathogenic	0.9035	pathogenic	-0.379	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
K/D	0.8661	likely_pathogenic	0.9217	pathogenic	0.171	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
K/E	0.4271	ambiguous	0.4088	ambiguous	0.199	Stabilizing	0.999	D	0.578	neutral	N	0.454264779	None	None	I
K/F	0.9112	likely_pathogenic	0.9386	pathogenic	-0.219	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	I
K/G	0.719	likely_pathogenic	0.8092	pathogenic	-0.311	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	I
K/H	0.4484	ambiguous	0.5182	ambiguous	-0.515	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
K/I	0.613	likely_pathogenic	0.698	pathogenic	0.424	Stabilizing	1.0	D	0.696	prob.neutral	N	0.49237478	None	None	I
K/L	0.5943	likely_pathogenic	0.6723	pathogenic	0.424	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	I
K/M	0.4243	ambiguous	0.5139	ambiguous	0.148	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	I
K/N	0.7061	likely_pathogenic	0.8016	pathogenic	0.047	Stabilizing	1.0	D	0.652	neutral	N	0.498946445	None	None	I
K/P	0.9686	likely_pathogenic	0.9763	pathogenic	0.282	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
K/Q	0.2104	likely_benign	0.2776	benign	-0.088	Destabilizing	1.0	D	0.638	neutral	N	0.49069163	None	None	I
K/R	0.0934	likely_benign	0.1015	benign	-0.088	Destabilizing	0.999	D	0.537	neutral	N	0.48436784	None	None	I
K/S	0.6059	likely_pathogenic	0.719	pathogenic	-0.491	Destabilizing	0.999	D	0.616	neutral	None	None	None	None	I
K/T	0.2906	likely_benign	0.3691	ambiguous	-0.301	Destabilizing	1.0	D	0.656	neutral	N	0.400884572	None	None	I
K/V	0.574	likely_pathogenic	0.6627	pathogenic	0.282	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	I
K/W	0.8668	likely_pathogenic	0.899	pathogenic	-0.208	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
K/Y	0.8223	likely_pathogenic	0.8651	pathogenic	0.139	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	I

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.