TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20284	61075;61076;61077	chr2:178590875;178590874;178590873	chr2:179455602;179455601;179455600
N2AB	18643	56152;56153;56154	chr2:178590875;178590874;178590873	chr2:179455602;179455601;179455600
N2A	17716	53371;53372;53373	chr2:178590875;178590874;178590873	chr2:179455602;179455601;179455600
N2B	11219	33880;33881;33882	chr2:178590875;178590874;178590873	chr2:179455602;179455601;179455600
Novex-1	11344	34255;34256;34257	chr2:178590875;178590874;178590873	chr2:179455602;179455601;179455600
Novex-2	11411	34456;34457;34458	chr2:178590875;178590874;178590873	chr2:179455602;179455601;179455600
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-35
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2837
• 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
T/A	None	None	0.046	N	0.111	0.165	0.193865811164	gnomAD-4.0.0	1.44039E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.44375E-05	0	3.66327E-05

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
T/A	0.1504	likely_benign	0.1992	benign	-0.668	Destabilizing	0.046	N	0.111	neutral	N	0.478249001	None	None	N
T/C	0.564	likely_pathogenic	0.6084	pathogenic	-0.429	Destabilizing	0.999	D	0.412	neutral	None	None	None	None	N
T/D	0.6596	likely_pathogenic	0.7367	pathogenic	-0.564	Destabilizing	0.919	D	0.373	neutral	None	None	None	None	N
T/E	0.6619	likely_pathogenic	0.7539	pathogenic	-0.597	Destabilizing	0.919	D	0.361	neutral	None	None	None	None	N
T/F	0.5794	likely_pathogenic	0.6506	pathogenic	-0.86	Destabilizing	0.996	D	0.488	neutral	None	None	None	None	N
T/G	0.3068	likely_benign	0.3641	ambiguous	-0.889	Destabilizing	0.702	D	0.406	neutral	None	None	None	None	N
T/H	0.5148	ambiguous	0.5831	pathogenic	-1.237	Destabilizing	0.999	D	0.485	neutral	None	None	None	None	N
T/I	0.6272	likely_pathogenic	0.7317	pathogenic	-0.18	Destabilizing	0.984	D	0.351	neutral	N	0.505191573	None	None	N
T/K	0.4932	ambiguous	0.621	pathogenic	-0.796	Destabilizing	0.919	D	0.37	neutral	None	None	None	None	N
T/L	0.2292	likely_benign	0.297	benign	-0.18	Destabilizing	0.919	D	0.362	neutral	None	None	None	None	N
T/M	0.1596	likely_benign	0.2037	benign	0.209	Stabilizing	0.999	D	0.409	neutral	None	None	None	None	N
T/N	0.2322	likely_benign	0.2824	benign	-0.684	Destabilizing	0.896	D	0.381	neutral	N	0.505880438	None	None	N
T/P	0.7745	likely_pathogenic	0.8285	pathogenic	-0.312	Destabilizing	0.984	D	0.348	neutral	N	0.505191573	None	None	N
T/Q	0.4455	ambiguous	0.5396	ambiguous	-0.948	Destabilizing	0.988	D	0.382	neutral	None	None	None	None	N
T/R	0.4099	ambiguous	0.532	ambiguous	-0.46	Destabilizing	0.976	D	0.352	neutral	None	None	None	None	N
T/S	0.1304	likely_benign	0.1492	benign	-0.875	Destabilizing	0.046	N	0.097	neutral	N	0.436327139	None	None	N
T/V	0.4158	ambiguous	0.5089	ambiguous	-0.312	Destabilizing	0.919	D	0.37	neutral	None	None	None	None	N
T/W	0.8505	likely_pathogenic	0.878	pathogenic	-0.804	Destabilizing	0.999	D	0.566	neutral	None	None	None	None	N
T/Y	0.6349	likely_pathogenic	0.6967	pathogenic	-0.571	Destabilizing	0.996	D	0.491	neutral	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.