TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20136	60631;60632;60633	chr2:178591319;178591318;178591317	chr2:179456046;179456045;179456044
N2AB	18495	55708;55709;55710	chr2:178591319;178591318;178591317	chr2:179456046;179456045;179456044
N2A	17568	52927;52928;52929	chr2:178591319;178591318;178591317	chr2:179456046;179456045;179456044
N2B	11071	33436;33437;33438	chr2:178591319;178591318;178591317	chr2:179456046;179456045;179456044
Novex-1	11196	33811;33812;33813	chr2:178591319;178591318;178591317	chr2:179456046;179456045;179456044
Novex-2	11263	34012;34013;34014	chr2:178591319;178591318;178591317	chr2:179456046;179456045;179456044
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-120
• Domain position: 57
• Structural Position: 138
• Q(SASA): 0.0616
• 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/H	rs1060500492	-3.055	1.0	D	0.888	0.772	0.920432766518	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
L/H	rs1060500492	-3.055	1.0	D	0.888	0.772	0.920432766518	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
L/H	rs1060500492	-3.055	1.0	D	0.888	0.772	0.920432766518	gnomAD-4.0.0	8.97353E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.67633E-05	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	0.9317	likely_pathogenic	0.9414	pathogenic	-2.49	Highly Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
L/C	0.8683	likely_pathogenic	0.8816	pathogenic	-1.629	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.218	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/E	0.9978	likely_pathogenic	0.9986	pathogenic	-2.892	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/F	0.344	ambiguous	0.4411	ambiguous	-1.501	Destabilizing	1.0	D	0.797	deleterious	N	0.512810983	None	None	N
L/G	0.99	likely_pathogenic	0.9929	pathogenic	-3.076	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/H	0.9858	likely_pathogenic	0.9925	pathogenic	-2.953	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.570303753	None	None	N
L/I	0.2236	likely_benign	0.2214	benign	-0.705	Destabilizing	0.999	D	0.648	neutral	N	0.502251145	None	None	N
L/K	0.9935	likely_pathogenic	0.9961	pathogenic	-1.879	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/M	0.3172	likely_benign	0.3311	benign	-0.979	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
L/N	0.9973	likely_pathogenic	0.9983	pathogenic	-2.672	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
L/P	0.9971	likely_pathogenic	0.9981	pathogenic	-1.295	Destabilizing	1.0	D	0.909	deleterious	D	0.570303753	None	None	N
L/Q	0.986	likely_pathogenic	0.9909	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/R	0.9838	likely_pathogenic	0.9895	pathogenic	-2.171	Highly Destabilizing	1.0	D	0.9	deleterious	D	0.570303753	None	None	N
L/S	0.9943	likely_pathogenic	0.9961	pathogenic	-3.098	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/T	0.9806	likely_pathogenic	0.985	pathogenic	-2.604	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/V	0.289	likely_benign	0.284	benign	-1.295	Destabilizing	0.999	D	0.657	neutral	D	0.529029134	None	None	N
L/W	0.9303	likely_pathogenic	0.9608	pathogenic	-1.824	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/Y	0.9139	likely_pathogenic	0.9529	pathogenic	-1.677	Destabilizing	1.0	D	0.856	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.