TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13800	41623;41624;41625	chr2:178636173;178636172;178636171	chr2:179500900;179500899;179500898
N2AB	12159	36700;36701;36702	chr2:178636173;178636172;178636171	chr2:179500900;179500899;179500898
N2A	11232	33919;33920;33921	chr2:178636173;178636172;178636171	chr2:179500900;179500899;179500898
N2B	4735	14428;14429;14430	chr2:178636173;178636172;178636171	chr2:179500900;179500899;179500898
Novex-1	4860	14803;14804;14805	chr2:178636173;178636172;178636171	chr2:179500900;179500899;179500898
Novex-2	4927	15004;15005;15006	chr2:178636173;178636172;178636171	chr2:179500900;179500899;179500898
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-88
• Domain position: 21
• Structural Position: 30
• Q(SASA): 0.0936
• 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
L/S	None	None	0.998	D	0.888	0.482	0.705181888856	gnomAD-4.0.0	6.8496E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00174E-07	0	0
L/W	rs2060414501	None	1.0	D	0.839	0.455	0.700816104296	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/W	rs2060414501	None	1.0	D	0.839	0.455	0.700816104296	gnomAD-4.0.0	2.48176E-06	None	None	None	None	N	None	1.33615E-05	0	None	0	0	None	1.56499E-05	0	1.6968E-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
L/A	0.9768	likely_pathogenic	0.9865	pathogenic	-1.769	Destabilizing	0.992	D	0.741	deleterious	None	None	None	None	N
L/C	0.9663	likely_pathogenic	0.98	pathogenic	-1.123	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9997	pathogenic	-1.624	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/E	0.9973	likely_pathogenic	0.9981	pathogenic	-1.366	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/F	0.5119	ambiguous	0.6785	pathogenic	-0.929	Destabilizing	0.997	D	0.735	deleterious	N	0.356360212	None	None	N
L/G	0.996	likely_pathogenic	0.9973	pathogenic	-2.301	Highly Destabilizing	0.999	D	0.902	deleterious	None	None	None	None	N
L/H	0.9886	likely_pathogenic	0.993	pathogenic	-1.716	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/I	0.2977	likely_benign	0.3896	ambiguous	-0.235	Destabilizing	0.983	D	0.615	neutral	None	None	None	None	N
L/K	0.9927	likely_pathogenic	0.9941	pathogenic	-1.145	Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
L/M	0.3993	ambiguous	0.4899	ambiguous	-0.362	Destabilizing	0.948	D	0.46	neutral	N	0.436299967	None	None	N
L/N	0.9977	likely_pathogenic	0.9983	pathogenic	-1.609	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/P	0.9982	likely_pathogenic	0.9987	pathogenic	-0.727	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/Q	0.9862	likely_pathogenic	0.9902	pathogenic	-1.335	Destabilizing	0.999	D	0.89	deleterious	None	None	None	None	N
L/R	0.9843	likely_pathogenic	0.9881	pathogenic	-1.203	Destabilizing	0.999	D	0.88	deleterious	None	None	None	None	N
L/S	0.9962	likely_pathogenic	0.9979	pathogenic	-2.317	Highly Destabilizing	0.998	D	0.888	deleterious	D	0.534690513	None	None	N
L/T	0.9864	likely_pathogenic	0.9918	pathogenic	-1.89	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
L/V	0.4451	ambiguous	0.5814	pathogenic	-0.727	Destabilizing	0.543	D	0.38	neutral	N	0.419976553	None	None	N
L/W	0.9634	likely_pathogenic	0.9816	pathogenic	-1.203	Destabilizing	1.0	D	0.839	deleterious	D	0.534241836	None	None	N
L/Y	0.9615	likely_pathogenic	0.9787	pathogenic	-0.864	Destabilizing	1.0	D	0.794	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.